Germline Profiling and Molecular Characterization of Early Onset Metastatic Colorectal Cancer
BackgroundEarly onset colorectal cancer (EO CRC) is a heterogeneous colorectal cancer subtype with obvious hereditary tendencies and increasing incidence. We sought to determine the susceptibility genes and molecular characteristics of EO CRC.Methods330 EO metastatic CRC (mCRC) (≤55 years) and 110 average-onset (AO) mCRC patients (>55 years) were enrolled. Capture-based targeted sequencing was performed on tumor tissue and paired white blood cells using a sequencing panel of 520 genes. The association between molecular alterations and overall survival (OS) was analyzed.ResultsOf the 330 EO mCRC patients, 31 carried p...
Source: Frontiers in Oncology - October 19, 2020 Category: Cancer & Oncology Source Type: research

Genetic Gastric Cancer Risk Syndromes
AbstractPurpose of reviewGastric cancer is a leading cause of cancer death in the world. Between 1 and 3% of cases are associated with specific genetic cancer risk syndromes. The purpose of this article is to review the latest insights, as well as gaps in knowledge, regarding some of the most common hereditary gastric cancer syndromes: hereditary diffuse gastric cancer (HDGC), gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), Lynch syndrome, the adenomatous polyposis syndromes, and the hamartomatous polyposis syndromes.Recent findingsPatients carrying pathogenic variants inCDH1, but not meeting clinical...
Source: Current Treatment Options in Gastroenterology - October 19, 2020 Category: Gastroenterology Source Type: research

Insertion of an Alu ‐like element in MLH1 intron 7 as a novel cause of Lynch syndrome
ConclusionsThe insertion of a truncated AluSx like element intoMLH1 intron 7 results in aberrant splicing and transcription, thereby causing Lynch syndrome. This study confirms that retrotransposon insertions may be an important mechanism for cancer predisposition. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - October 15, 2020 Category: Genetics & Stem Cells Authors: Yirong Li, Erin Salo ‐Mullen, Anna Varghese, Magan Trottier, Zsofia K. Stadler, Liying Zhang Tags: ORIGINAL ARTICLE Source Type: research

DNA Mismatch Repair–deficient Endometrial Carcinosarcomas Portend Distinct Clinical, Morphologic, and Molecular Features Compared With Traditional Carcinosarcomas
Uterine carcinosarcomas (UCSs) are aggressive neoplasms composed of high-grade malignant epithelial and mesenchymal elements with most (∼90%) showing TP53 abnormalities. A subset, however, shows mismatch repair deficiency (MMR-D). We sought to describe their clinical, morphologic, and molecular features. Clinicopathologic data of MMR-D UCSs were recorded including age, stage, follow-up, mismatch repair and p53 immunohistochemistry (IHC), MLH1 promoter methylation status, and germline alterations, TP53 mutation status, microsatellite instability and mutational burden by massively parallel sequencing. Seventeen (6.2%) MM...
Source: The American Journal of Surgical Pathology - October 14, 2020 Category: Pathology Tags: Original Articles Source Type: research

Germline multigene panel testing revealed a BRCA2 pathogenic variant in a patient with suspected Lynch syndrome
AbstractThere has been a rapid advance in germline multigene panel testing by next-generation sequencing, and it is being widely used in clinical settings. A 56-year-old woman suspected of having Lynch syndrome was identified as aBRCA2 pathogenic variant carrier by multigene panel testing. The patient was diagnosed with endometrial cancer at the age of 39  years, and total laparoscopic hysterectomy and bilateral salpingectomy were performed at the age of 49 years; however, bilateral oophorectomy was not performed at that time. As she had a family history of colorectal cancer and a history of endometrial cancer, L...
Source: International Cancer Conference Journal - October 9, 2020 Category: Cancer & Oncology Source Type: research

Discordant DNA mismatch repair protein status between synchronous or metachronous gastrointestinal carcinomas: frequency, patterns, and molecular etiologies
This study aims at examining the frequency, patterns and molecular etiologies of such inter-tumoral MMR discordances. We analyzed a cohort of 2159 colorectal cancer (CRC) patients collected over a 5-year period and found that 1.3% of the patients (27/2159) had  ≥ 2 primary CRCs, and 25.9% of the patients with ≥ 2 primary CRCs (7/27) exhibited inter-tumoral MMR discordance. We then combined the seven MMR-discordant CRC patients with three additional MMR-discordant GIT carcinoma patients and evaluated their discordant patterns and associated mol ecular abnormalities. The 10 patients consiste...
Source: Familial Cancer - October 9, 2020 Category: Cancer & Oncology Source Type: research

Clinicopathologic characteristics and outcomes of endometrial Cancer patients with mismatch repair deficiency in the era of universal Lynch syndrome screening.
Abstract OBJECTIVE: To evaluate clinicopathologic characteristics and survival impact associated with mismatch repair (MMR) deficient subgroups of endometrial cancer (EC) in patients undergoing universal screening for Lynch Syndrome. METHODS: A retrospective cohort study using a prospectively maintained gynecologic oncology registry of patients who underwent surgery for EC was conducted. All pathology specimens underwent tumor testing using immunohistochemistry for MMR deficiency with reflex MLH1 promotor methylation testing. Tumors were classified as MMR-I (intact MMR expression), MMR-DM (MMR deficient due t...
Source: Gynecologic Oncology - October 9, 2020 Category: Cancer & Oncology Authors: Carr C, Son J, Yao M, Priyadarshini A, Marquard J, Vargas R, Michener C, AlHilli MM Tags: Gynecol Oncol Source Type: research

Variable Expression of MSH6 in Endometrial Carcinomas With Intact Mismatch Repair and With MLH1 Loss Due to MLH1 Methylation
Immunohistochemistry for mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 is an effective screen to detect individuals at risk for Lynch syndrome. College of American Pathologists guidelines stipulate that protein expression should be reported as present versus absent, as most patients with germline mutations in a mismatch repair gene have complete loss of protein expression in tumor cells. A similar approach is employed to screen for cancer patients eligible for immune checkpoint blockade. This “all or none” interpretive approach ignores substantial evidence that mismatch repair may be more finely regulated...
Source: International Journal of Gynecological Pathology - October 8, 2020 Category: Pathology Tags: PATHOLOGY OF THE CORPUS: ORIGINAL ARTICLES Source Type: research

Implementation of Universal Colorectal Cancer Screening for Lynch Syndrome in Hispanics Living in Puerto Rico
ConclusionsOur data is consistent with the results from other studies including US Hispanics, where approximately 10% of Hispanic individuals with colorectal cancer have microsatellite instability. Our results support universal tumor-based screening for LS among Hispanics in accordance with National Comprehensive Cancer Network guidelines. (Source: Journal of Racial and Ethnic Health Disparities)
Source: Journal of Racial and Ethnic Health Disparities - October 1, 2020 Category: International Medicine & Public Health Source Type: research

Cancers, Vol. 12, Pages 2803: Complete Loss of EPCAM Immunoexpression Identifies EPCAM Deletion Carriers in MSH2-Negative Colorectal Neoplasia
bel Trias José Ignacio Busteros Gemma Mateu Francesc Balaguer María-Teresa Fernández-Figueras Manel Esteller Eva Musulén The use of epithelial cell adhesion molecule (EPCAM) immunohistochemistry (IHC) is not included in the colorectal cancer (CRC) screening algorithm to detect Lynch syndrome (LS) patients. The aim of the present study was to demonstrate that EPCAM IHC is a useful tool to guide the LS germ-line analysis when a loss of MSH2 expression was present. We retrospectively studied MSH2 and EPCAM IHC in a large series of 190 lesions composed of malignant neoplasms (102), p...
Source: Cancers - September 28, 2020 Category: Cancer & Oncology Authors: M íriam Cuatrecasas I ñigo Gorostiaga Cristina Riera Esteban Saperas Gemma Llort Irmgard Costa Xavier Matias-Guiu Cristina Carrato Matilde Navarro Marta Pineda N úria Dueñas Joan Brunet Vicente Marco Isabel Trias Jos é Ignacio Busteros Gemma Mateu Fr Tags: Article Source Type: research

Predicting the rising incidence and mortality of endometrial cancers among women aged 65-74 years in Catalonia
Cancers of the endometrium rank as the fourth most frequently diagnosed cancers among European women [1]. Endometrial cancer is the most common type, representing 90% of the cancers of the corpus uteri. Endometrial cancers are mostly diagnosed after menopause and hormones play a key role in their etiology [2]. Established risk factors include early menarche, late menopause, nulliparity, menopausal hormone use, obesity, diabetes, hypertension and Lynch syndrome [2 –5]. (Source: Maturitas)
Source: Maturitas - September 28, 2020 Category: Primary Care Authors: Jon Frias-Gomez, Paula Peremiquel-Trillas, Laia Alemany, Alberto Ameijide, Rafael Marcos-Gragera, Jordi Ponce, Joan Brunet, Xavier Matias-Guiu, Jaume Galceran, Ángel Izquierdo, Josep M. Borràs, Laura Costas, Ramon Clèries Source Type: research

Patients with unexplained mismatch repair deficiency are interested in updated genetic testing
ConclusionsUpdated risk assessment and genetic counseling with a discussion of the benefits and limitations of germline and somatic genetic testing, is essential as the understanding of UMMRD and genetic testing recommendations for this population evolve. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - September 20, 2020 Category: Cancer & Oncology Source Type: research

European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender.
CONCLUSION: The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented. PMID: 32956497 [PubMed - as supplied by publisher] (Source: The British Journal of Surgery)
Source: The British Journal of Surgery - September 20, 2020 Category: Surgery Authors: Seppälä TT, Latchford A, Negoi I, Sampaio Soares A, Jimenez-Rodriguez R, Sánchez-Guillén L, Evans DG, Ryan N, Crosbie EJ, Dominguez-Valentin M, Burn J, Kloor M, von Knebel Doeberitz M, van Duijnhoven FJB, Quirke P, Sampson JR, Møller P, Möslein G, E Tags: Br J Surg Source Type: research

Quantitative evaluation of MSI testing using NGS detects the imperceptible microsatellite changed caused by MSH6 deficiency
AbstractMicrosatellite instability (MSI) is an effective biomarker for diagnosing Lynch syndrome (LS) and predicting the responsiveness of cancer therapy. MSI testing is conventionally performed by capillary electrophoresis, and MSI status is judged by visual assessment of allele size change. Here, we attempted to develop a quantitative evaluation model of MSI using next-generation sequencing (NGS). Microsatellite markers were analyzed in tumor and non-tumor tissues of colorectal cancer patients by NGS after a single multiplex polymerase chain reaction amplification. The read counts corresponding to microsatellite loci len...
Source: Familial Cancer - September 18, 2020 Category: Cancer & Oncology Source Type: research

Prophylactic Gynecologic Surgery at Time of Colectomy Benefits Women with Lynch Syndrome and Colon Cancer: A Markov Cost-Effectiveness Analysis
CONCLUSIONS: Total abdominal colectomy with prophylactic hysterectomy at 30 years of age was the most cost-effective surgical choice in women with Lynch syndrome and colon cancer. The addition of bilateral salpingo-oophorectomy offered the highest event-free survival and lowest mortality. However, the additional morbidity of premature menopause of prophylactic salpingo-oophorectomy for younger women outweighed the benefit of ovarian cancer prevention. See Video Abstract at http://links.lww.com/DCR/B287. LA CIRUGÍA GINECOLÓGICA PROFILÁCTICA EN EL MOMENTO DE LA COLECTOMÍA BENEFICIA A LAS MUJERE...
Source: Diseases of the Colon and Rectum - September 18, 2020 Category: Gastroenterology Tags: Original Contributions: Colorectal Cancer Source Type: research

Implementing Cancer Genomics in State Health Agencies: Mapping Activities to an Implementation Science Outcome Framework
Conclusion: State health agencies can use the Doyle et al. [Genet Med. 2018;20(9):995 –1003] performance objectives and outcome measures to evaluate proposed and ongoing activities. By demonstrating whether activities result in improved outcomes, state health agencies can build the evidence for the implementation of cancer genomics activities.Public Health Genomics (Source: Public Health Genomics)
Source: Public Health Genomics - September 17, 2020 Category: Genetics & Stem Cells Source Type: research

The proportion of endometrial tumours associated with Lynch syndrome (PETALS): A prospective cross-sectional study
by Neil A. J. Ryan, Raymond McMahon, Simon Tobi, Tristan Snowsill, Shona Esquibel, Andrew J. Wallace, Sancha Bunstone, Naomi Bowers, Ioana E. Mosneag, Sarah J. Kitson, Helena O ’Flynn, Neal C. Ramchander, Vanitha N. Sivalingam, Ian M. Frayling, James Bolton, Rhona J. McVey, D. Gareth Evans, Emma J. Crosbie BackgroundLynch syndrome (LS) predisposes to endometrial cancer (EC), colorectal cancer, and other cancers through inherited pathogenic variants affecting mismatch-repair (MMR) genes. Diagnosing LS in women with EC can reduce subsequent cancer mortality through colonoscopic surveillance and aspirin chemoprevention;...
Source: PLoS Medicine - September 16, 2020 Category: Internal Medicine Authors: Neil A. J. Ryan Source Type: research

Diet quality and colorectal tumor risk in persons with Lynch syndrome
Publication date: December 2020Source: Cancer Epidemiology, Volume 69Author(s): Anouk H. Eijkelboom, Jesca G.M. Brouwer, Hans F.A. Vasen, Tanya M. Bisseling, Jan J. Koornstra, Ellen Kampman, Fränzel J.B. van Duijnhoven (Source: Cancer Epidemiology)
Source: Cancer Epidemiology - September 15, 2020 Category: Cancer & Oncology Source Type: research

Worldwide variation in lynch syndrome screening: case for universal screening in low colorectal cancer prevalence areas
AbstractTo perform a systematic assessment of universal Lynch syndrome (LS) screening yield in colorectal cancer (CRC) patients around the world. Universal screening for LS is recommended in all CRC patients. However, the variation in yield of LS screening in the setting of significant global variation in CRC prevalence is unknown. A systematic review of articles in the MEDLINE database was performed to identify studies performing universal screening for LS. All cases with microsatellite instability (MSI-H) or missing one or more proteins on immunohistochemistry (IHC) were considered screening positive. The overall pooled ...
Source: Familial Cancer - September 10, 2020 Category: Cancer & Oncology Source Type: research

Ovarian cancer risk in Lynch syndrome: It's time to individualize.
Abstract Our understanding of cancer risks associated with Lynch syndrome (LS) has evolved since Dr. Warthin first identified family G in 1913. The current study by Ryan et al provides insight into provider and patient knowledge about gynecologic cancer care options in LS and found that counseling, surveillance, and risk reduction (RR) for these patients vary widely across providers in the UK (BJOG 2020 xxxx). The current study highlights two important points regarding care in LS. PMID: 32892474 [PubMed - as supplied by publisher] (Source: BJOG : An International Journal of Obstetrics and Gynaecology)
Source: BJOG : An International Journal of Obstetrics and Gynaecology - September 4, 2020 Category: OBGYN Authors: Ring KL Tags: BJOG Source Type: research

Effect of chemoprevention by low-dose aspirin of new or recurrent colorectal adenomas in patients with Lynch syndrome (AAS-Lynch): study protocol for a multicenter, double-blind, placebo-controlled randomized controlled trial
Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC) and confers a high lifetime risk of CRC estimated to be up to 60%. Colonoscopy is recommended every 2  years in LS patients abov... (Source: Trials)
Source: Trials - September 4, 2020 Category: General Medicine Authors: Adil Soualy, David Deutsch, Mourad Benallaoua, Amal Ait-Omar, Florence Mary, Sabine Helfen, Marouane Boubaya, Vincent Levy and Robert Benamouzig Tags: Study protocol Source Type: research

Universal tumor screening for lynch syndrome: perspectives of patients regarding willingness and informed consent
Personalized Medicine, Ahead of Print. (Source: Future Medicine: Personalized Medicine)
Source: Future Medicine: Personalized Medicine - September 1, 2020 Category: Genetics & Stem Cells Authors: Anusree Subramonian Doug Smith Elizabeth Dicks Lesa Dawson Mark Borgaonkar Holly Etchegary Source Type: research

Aspirin Protects Against Colorectal Cancer in Lynch Syndrome
Daily aspirin use for at least 2 years significantly reduced colorectal cancer risk among patients with Lynch syndrome, according to the 10-year follow-up of a randomized trial. Aspirin ’s protective effect did not become apparent until about 5 years after beginning treatment, the investigators reported in The Lancet. (Source: JAMA)
Source: JAMA - August 25, 2020 Category: General Medicine Source Type: research

Cancers, Vol. 12, Pages 2407: Genetic Susceptibility to Endometrial Cancer: Risk Factors and Clinical Management
s C. Fleisch Endometrial cancer (EC) is the most common cancer affecting the female reproductive organs in higher-income states. Apart from reproductive factors and excess weight, genetic predisposition is increasingly recognized as a major factor in endometrial cancer risk. Endometrial cancer is genetically heterogeneous: while a subgroup of patients belongs to cancer predisposition syndromes (most notably the Lynch Syndrome) with high to intermediate lifetime risks, there are also several common genomic polymorphisms contributing to the spectrum of germline predispositions. Germline variants and somatic events may ac...
Source: Cancers - August 24, 2020 Category: Cancer & Oncology Authors: Thilo D örk Peter Hillemanns Clemens Tempfer Julius Breu Markus C. Fleisch Tags: Review Source Type: research

Comparison of Molecular, Clinicopathological, and Pedigree Differences Between Lynch-Like and Lynch Syndromes
In conclusion, LLS should be classified as a mixed entity, containing cases of LS, other hereditary cancer syndromes, and sporadic CRC. The high risks of CRC and extra-CRCs, which were found in this study, suggest tailored management policy and surveillance should be formulated based on individual and family risk. The surveillance regimen can be based on the presence of confirmed pathogenic/likely pathogenic germline variant(s) and family history. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - August 18, 2020 Category: Genetics & Stem Cells Source Type: research

Height and Colorectal and Endometrial Cancer Risk for Persons with Lynch Syndrome.
Abstract Persons with Lynch syndrome (LS - carrying a pathogenic mutation in a DNA mismatch repair gene) have an increased colorectal cancer (CRC) and endometrial cancer (EC) risk. A high reported variability in cancer risk suggests the existence of factors that modify cancer risk for LS. We aimed to investigate the association between height and CRC and EC for persons with LS using two large studies. Information of 1,213 men and 1,636 women with LS from the Colon Cancer Family Registry (1998-2007) and the GEOLynch cohort study (2006-2017) was harmonized. We used weighted Cox proportional hazard regression models ...
Source: Am J Epidemiol - August 16, 2020 Category: Epidemiology Authors: Brouwer JGM, Newcomb PA, Bisseling TM, Figueiredo JC, Hopper JL, Jenkins MA, Koornstra JJ, Lindor NM, Vasen HFA, Win AK, Kampman E, van Duijnhoven FJB Tags: Am J Epidemiol Source Type: research

A Lynch syndrome-associated mutation at a Bergerat ATP-binding fold destabilizes the structure of the DNA mismatch repair endonuclease MutL [DNA and Chromosomes]
In humans, mutations in genes encoding homologs of the DNA mismatch repair endonuclease MutL cause a hereditary cancer that is known as Lynch syndrome. Here, we determined the crystal structures of the N-terminal domain (NTD) of MutL from the thermophilic eubacterium Aquifex aeolicus (aqMutL) complexed with ATP analogs at 1.69–1.73 Å. The structures revealed significant structural similarities to those of a human MutL homolog, postmeiotic segregation increased 2 (PMS2). We introduced five Lynch syndrome-associated mutations clinically found in human PMS2 into the aqMutL NTD and investigated the protein stabilit...
Source: Journal of Biological Chemistry - August 13, 2020 Category: Chemistry Authors: Keisuke Izuhara, Kenji Fukui, Takeshi Murakawa, Seiki Baba, Takashi Kumasaka, Kazuhisa Uchiyama, Takato Yano Tags: Molecular Bases of Disease Source Type: research

Updates in the field of hereditary nonpolyposis colorectal cancer.
Authors: Peltomäki P, Olkinuora A, Nieminen TT Abstract INTRODUCTION: Up to one third of colorectal cancers show familial clustering and 5% are hereditary single-gene disorders. Hereditary non-polyposis colorectal cancer comprises DNA mismatch repair-deficient and -proficient subsets, represented by Lynch syndrome (LS) and familial colorectal cancer type X (FCCTX), respectively. Accurate knowledge of molecular etiology and genotype-phenotype correlations are critical for tailored cancer prevention and treatment. AREAS COVERED: The authors highlight advances in the molecular dissection of hereditary non-pol...
Source: Expert Review of Gastroenterology and Hepatology - August 13, 2020 Category: Gastroenterology Tags: Expert Rev Gastroenterol Hepatol Source Type: research

Universal Mismatch Repair Protein Screening in Upper Tract Urothelial Carcinoma.
CONCLUSIONS: The rate of MMR loss observed in UTUC was comparable to that in the established setting of colorectal and endometrial adenocarcinomas, supporting universal UTUC screening at our institution and others. PMID: 32789450 [PubMed - as supplied by publisher] (Source: American Journal of Clinical Pathology)
Source: American Journal of Clinical Pathology - August 12, 2020 Category: Pathology Authors: Gayhart MG, Johnson N, Paul A, Quillin JM, Hampton LJ, Idowu MO, Smith SC Tags: Am J Clin Pathol Source Type: research

Gastric cancer is highly prevalent in Lynch syndrome patients with atrophic gastritis
ConclusionLS patients, particularly those with atrophic gastritis, are at high risk of gastric neoplasm and often develop multiple tumors. Endoscopic surveillance for gastric cancer is recommended for LS patients, especially those with atrophic gastritis. (Source: Gastric Cancer)
Source: Gastric Cancer - August 12, 2020 Category: Gastroenterology Source Type: research

Colorectal Cancer: Microsatellite Instability/Mismatch Repair Testing in the Era of Digital Pathology
It has been>15 years since universal microsatellite instability (MSI) or mismatch repair (MMR) testing has been recommend for all cases of colorectal carcinoma.1 MSI/MMR testing is a proven prognostic marker and can help identify patients with possible hereditary cancers (Lynch syndrome).2,3 More recently, checkpoint inhibition therapy has been found to be effective in tumors that demonstrate MSI, making MSI/MMR testing a pan-cancer therapeutic biomarker.4 Given its importance, multiple organizations, including the American Society of Clinical Oncology, Association for Molecular Pathology, College of American Pathologis...
Source: Gastroenterology - August 11, 2020 Category: Gastroenterology Authors: Aaron Pollett Tags: Editorial Source Type: research

Cancers, Vol. 12, Pages 2225: Risk of Cancer in Family Members of Patients with Lynch-Like Syndrome
mon y Cajal Alexandra Gisbert-Beamud Joaquin Cubiella Laura Rivas Maite Herraiz Catalina Garau Inmaculada Salces Marta Carrillo-Palau Luis Bujanda Adriá López-Fernández Cristina Alvarez-Urturi María Jesús López Cristina Alenda Pedro Zapater Francisco Javier Lacueva Francesc Balaguer Jose-Luis Soto Óscar Murcia Rodrigo Jover Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC patients develop mismatch repair deficiency without germline pathogenic mutation, known as Lynch-like syndrome (LLS). We compared...
Source: Cancers - August 8, 2020 Category: Cancer & Oncology Authors: Mar ía Dolores Picó Ana Beatriz S ánchez-Heras Adela Castillejo Mar Giner-Calabuig Miren Alustiza Ariadna S ánchez Leticia Moreira Mar ía Pellise Antoni Castells Gemma Llort Carmen Yag üe Teresa Ramon y Cajal Alexandra Gisbert-Beamud Joaquin Cubiell Tags: Article Source Type: research

Is a colorectal neoplasm diagnosis a trigger to change dietary and other lifestyle habits for persons with Lynch syndrome? A prospective cohort study
AbstractA cancer diagnosis is suggested to be associated with changes in dietary and lifestyle habits. Whether this applies to persons with familial cancer, such as Lynch syndrome (LS) is unknown. We investigated whether a colorectal neoplasm (CRN) diagnosis in persons with LS is associated with changes in dietary and lifestyle habits over time. We used data of confirmed LS mutation carriers from the GEOLynch study, a prospective cohort study. Information on dietary intake and lifestyle habits was collected with a validated semi-quantitative food frequency questionnaire and a general questionnaire administered at baseline ...
Source: Familial Cancer - August 7, 2020 Category: Cancer & Oncology Source Type: research

Recent advances in Lynch syndrome
(Source: Familial Cancer)
Source: Familial Cancer - August 7, 2020 Category: Cancer & Oncology Source Type: research

Different surgical outcome and follow-up status between dMMR and pMMR colorectal cancer patients who fulfilled with Amsterdam-II criteria
Although hereditary non-polyposis colorectal cancer (HNPCC) could be subtyped into proficient or deficient mismatch repair gene expression (pMMR or dMMR), distinct clinical features between these two subgroups... (Source: World Journal of Surgical Oncology)
Source: World Journal of Surgical Oncology - August 7, 2020 Category: Cancer & Oncology Authors: Ci-Yuan Sun, Jy-Ming Chiang, Tse-Ching Chen, Hsin-Yun Hung and Jeng-Fu You Tags: Research Source Type: research

Recent advances in Lynch syndrome: response to M øller et al.
(Source: Familial Cancer)
Source: Familial Cancer - August 2, 2020 Category: Cancer & Oncology Source Type: research

Secondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA.
Authors: Piombino C, Cortesi L, Lambertini M, Punie K, Grandi G, Toss A Abstract BRCA1- and BRCA2-associated hereditary breast and ovarian cancer syndromes are among the best-known and most extensively studied hereditary cancer syndromes. Nevertheless, many patients who proved negative at BRCA genetic testing bring pathogenic mutations in other suppressor genes and oncogenes associated with hereditary breast and/or ovarian cancers. These genes include TP53 in Li-Fraumeni syndrome, PTEN in Cowden syndrome, mismatch repair (MMR) genes in Lynch syndrome, CDH1 in diffuse gastric cancer syndrome, STK11 in Peutz-Jeghers ...
Source: Journal of Oncology - August 2, 2020 Category: Cancer & Oncology Tags: J Oncol Source Type: research

A mismatch in care: results of a United Kingdom-wide patient and clinician survey of gynaecological services for women with Lynch syndrome.
CONCLUSIONS: There is widespread variation in the services offered to women with LS in the UK. As a community, gynaecological oncologists should move towards a nationally agreed provision of services. PMID: 32725920 [PubMed - as supplied by publisher] (Source: BJOG : An International Journal of Obstetrics and Gynaecology)
Source: BJOG : An International Journal of Obstetrics and Gynaecology - July 28, 2020 Category: OBGYN Authors: Ryan NAJ, Nobes M, Sedgewick D, Teoh SN, Evans DG, Crosbie EJ Tags: BJOG Source Type: research

Contribution of mRNA Splicing to Mismatch Repair Gene Sequence Variant Interpretation
Functional assays that assess mRNA splicing can be used in interpretation of the clinical significance of sequence variants, including the Lynch syndrome-associated mismatch repair (MMR) genes. The purpose of this study was to investigate the contribution of splicing assay data to the classification of MMR gene sequence variants. We assayed mRNA splicing for 24 sequence variants in MLH1, MSH2, and MSH6, including 12 missense variants that were also assessed using a cell-free in vitro MMR activity (CIMRA) assay. Multifactorial likelihood analysis was conducted for each variant, combining CIMRA outputs and clinical data wher...
Source: Frontiers in Genetics - July 26, 2020 Category: Genetics & Stem Cells Source Type: research

Genomic alterations in Turcot syndrome: Insights from whole exome sequencing
Turcot's syndrome (TS) was originally described as familial predisposition to cancer of the large bowel and brain [1], and is a phenotypic variant of Hereditary Non-Polyposis Colorectal Cancer (HNPCC). HNPCC is caused by germline mutations in one of the DNA mismatch-repair (MMR)-genes MLH1, PMS1, PMS2, MSH2, or MSH6. Identification of HNPCC is based upon clinicopathological features including MMR-deficiency determined by immunohistochemistry or microsatellite instability (MSI)-analysis. Lifetime brain tumor risk in HNPCC is 3%. (Source: Journal of the Neurological Sciences)
Source: Journal of the Neurological Sciences - July 23, 2020 Category: Neurology Authors: Philipp Karschnia, E. Zeynep Erson-Omay, Anita J. Huttner, Leon D. Kaulen, Daniel Duran, Robert K. Fulbright, Murat G ünel, Joachim M. Baehring Tags: Letter to the Editor Source Type: research

Evaluating the impact of universal Lynch syndrome screening in a publicly funded healthcare system
ConclusionThe implementation of universal screening in a publicly funded system will increase efficiency in detecting patients with LS. The resources available for genetic testing and counseling may be more limited in public systems, thus inclusion of secondary screening withBRAF andMLH1 promoter hypermethylation testing is key to further optimizing efficiency. (Source: Cancer Medicine)
Source: Cancer Medicine - July 22, 2020 Category: Cancer & Oncology Authors: Petra W. C. Lee, Angela C. Bedard, Setareh Samimi, Vivienne K. Beard, Quan Hong, James E. J. Bedard, Blake Gilks, David F. Schaeffer, Robert Wolber, Janice S. Kwon, Howard J. Lim, Sophie Sun, Kasmintan A. Schrader Tags: ORIGINAL RESEARCH Source Type: research

Correction: Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database
Genetics in Medicine, Published online: 20 July 2020; doi:10.1038/s41436-020-0892-4Correction: Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database (Source: Genetics in Medicine)
Source: Genetics in Medicine - July 19, 2020 Category: Genetics & Stem Cells Authors: Mev Dominguez-Valentin Julian R. Sampson Toni T. Sepp älä Sanne W. ten Broeke John-Paul Plazzer Sigve Nakken Christoph Engel Stefan Aretz Mark A. Jenkins Lone Sunde Inge Bernstein Gabriel Capella Francesc Balaguer Huw Thomas D. Gareth Evans John Burn Ma Source Type: research

Lynch syndrome identification in a Brazilian cohort of endometrial cancer screened by a universal approach.
CONCLUSION: This is the first report of the LS prevalence in EC screened by a universal approach in Brazil. Our findings contribute to a better understanding of the mutational landscape of this syndrome in Brazil, which is relevant for improved identification, genetic counseling, prevention and control of cancer in LS. PMID: 32694065 [PubMed - as supplied by publisher] (Source: Gynecologic Oncology)
Source: Gynecologic Oncology - July 17, 2020 Category: Cancer & Oncology Authors: Rosa RCA, Santis JO, Teixeira LA, Molfetta GA, Dos Santos JTT, Ribeiro VDS, Chahud F, Ribeiro-Silva A, Brunaldi MO, Silva WA, Ferraz VEF Tags: Gynecol Oncol Source Type: research

Dynamic human MutS{alpha}-MutL{alpha} complexes compact mismatched DNA [Biochemistry]
DNA mismatch repair (MMR) corrects errors that occur during DNA replication. In humans, mutations in the proteins MutSα and MutLα that initiate MMR cause Lynch syndrome, the most common hereditary cancer. MutSα surveilles the DNA, and upon recognition of a replication error it undergoes adenosine triphosphate-dependent conformational changes and recruits... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - July 13, 2020 Category: Science Authors: Kira C. Bradford, Hunter Wilkins, Pengyu Hao, Zimeng M. Li, Bangchen Wang, Dan Burke, Dong Wu, Austin E. Smith, Logan Spaller, Chunwei Du, Jacob W. Gauer, Edward Chan, Peggy Hsieh, Keith R. Weninger, Dorothy A. Erie Tags: Biological Sciences Source Type: research

Cancers, Vol. 12, Pages 1874: Cost-Effectiveness of Early Detection and Prevention Strategies for Endometrial Cancer —A Systematic Review
Cancers, Vol. 12, Pages 1874: Cost-Effectiveness of Early Detection and Prevention Strategies for Endometrial Cancer—A Systematic Review Cancers doi: 10.3390/cancers12071874 Authors: Gaby Sroczynski Artemisa Gogollari Annette Conrads-Frank Lára R. Hallsson Nora Pashayan Martin Widschwendter Uwe Siebert Endometrial cancer is the most common female genital tract cancer in developed countries. We systematically reviewed the current health-economic evidence on early detection and prevention strategies for endometrial cancer based on a search in relevant databases (Medline/Embase/Cochrane Librar...
Source: Cancers - July 10, 2020 Category: Cancer & Oncology Authors: Gaby Sroczynski Artemisa Gogollari Annette Conrads-Frank L ára R. Hallsson Nora Pashayan Martin Widschwendter Uwe Siebert Tags: Review Source Type: research

HPV nonrelated endocervical adenocarcinoma in hereditary cancer syndromes.
CONCLUSIONS: Our study confirms that gynecologic cancers including rare entities such as non-human papillomavirus-related endocervical cancer (NHPVA) are sentinels for inherited cancer syndromes. Endocervical cancer NHPVAs might be considered for cancer genetic counseling in order to improve cancer prevention. For this reason, the role of pathologists is particularly important for the correct identification of the cervical tumor site. PMID: 32635821 [PubMed - as supplied by publisher] (Source: Tumori)
Source: Tumori - July 10, 2020 Category: Cancer & Oncology Tags: Tumori Source Type: research

Neoadjuvant Immunotherapy-Based Systemic Treatment in MMR-Deficient or MSI-High Rectal Cancer: Case Series.
We report 3 cases of mismatch repair-deficient (dMMR) locally advanced adenocarcinoma of the rectum that showed significant response with neoadjuvant immunotherapy-based systemic treatment. The first patient was not eligible for standard therapy because of a history of radiotherapy to the prostate with concurrent comorbidities and therefore received single-agent pembrolizumab. The second patient did not respond to total neoadjuvant chemoradiation and subsequently received combined nivolumab and ipilimumab. The third patient had a known family history of Lynch syndrome and presented with locally advanced rectal cancer and a...
Source: Journal of the National Comprehensive Cancer Network : JNCCN - July 8, 2020 Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research

Cancers, Vol. 12, Pages 1848: Clinical and Molecular Assessment of Patients with Lynch Syndrome and Sarcomas Underpinning the Association with MSH2 Germline Pathogenic Variants
c Samuel Aguiar Junior Edenir Inez Palmero José Cláudio Casali-da-Rocha Dirce Maria Carraro Giovana Tardin Torrezan Lynch syndrome (LS) is a hereditary cancer-predisposing syndrome associated most frequently with epithelial tumors, particularly colorectal (CRC) and endometrial carcinomas (EC). The aim of this study was to investigate the relationship between sarcomas and LS by performing clinical and molecular characterization of patients presenting co-occurrence of sarcomas and tumors from the LS spectrum. We identified 27 patients diagnosed with CRC, EC, and other LS-associated tumors who had ...
Source: Cancers - July 8, 2020 Category: Cancer & Oncology Authors: Nath ália de Angelis de Carvalho Bianca Naomi Niitsuma Vanessa Nascimento Kozak Felipe D ’almeida Costa Mariana Petaccia de Macedo Bruna Elisa Catin Kupper Maria Let ícia Gobo Silva Maria Nirvana Formiga Sahlua Miguel Volc Samuel Aguiar Junior Edenir Tags: Article Source Type: research

A case of Turcot ’s syndrome type 1 with loss of immunoexpression of MSH6 in colon cancer and liver metastasis due to secondary somatic mutation in coding mononucleotide (C)8 tract: a case report
Lynch syndrome (LS), which is known as a hereditary cancer syndrome, is distinguished by microsatellite instability, represented by the altered number of repetitive sequences in the coding and/or non-coding re... (Source: BMC Medical Genetics)
Source: BMC Medical Genetics - July 1, 2020 Category: Genetics & Stem Cells Authors: Shintaro Akabane, Takao Hinoi, Kiwamu Akagi, Hideki Yamamoto, Haruki Sada, Yosuke Shimizu, Wataru Shimizu, Takeshi Sudo, Takashi Onoe, Kohei Ishiyama, Takahisa Suzuki, Hirofumi Tazawa, Naoto Hadano, Toshihiro Misumi, Masato Kojima, Haruna Kubota & hellip; Tags: Case report Source Type: research

Is tumor testing efficiency for Lynch syndrome different in rectal and colon cancer?
Tumor testing utility in Lynch syndrome (LS) diagnosis is established. (Source: Digestive and Liver Disease)
Source: Digestive and Liver Disease - June 29, 2020 Category: Gastroenterology Authors: Monica Marabelli, Sara Gandini, Paola Raviele Rafaniello, Mariarosaria Calvello, Gianluca Tolva, Irene Feroce, Matteo Lazzeroni, Elena Marino, Matteo Dal Molin, Cristina Trovato, Aliana Guerrieri-Gonzaga, Wanda Luisa Petz, Massimo Barberis, Lucio Bertario Tags: Oncology Source Type: research