A novel germline mutation in hMLH1 in three Korean women with endometrial cancer in a family of Lynch syndrome: case report and literature review
ConclusionThis report indicates a novel germline c.1367delC variant inMLH1, and presents a Korean case of uterine carcinosarcoma associated with Lynch syndrome. Furthermore, the c.1757_1758insC variant inMLH1 was suggested as a founder mutation in Lynch syndrome in Korean women. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - June 3, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Overview on population screening for carriers with germline mutations in mismatch repair (MMR) genes in China
(Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - May 17, 2021 Category: Cancer & Oncology Source Type: research

Overview on population screening for carriers with germline mutations in mismatch repair (MMR) genes in China
AbstractDNA mismatch repair (MMR) genes play an important role in maintaining genome stability. Germline mutations in MMR genes disrupt the mismatch repair function and cause genome instability. Carriers with MMR germline mutations are more likely to have MMR deficiency and microsatellite instability (MSI) than non-carriers and are prone to develop colorectal cancer (CRC) and extracolorectal malignancies, known as Lynch syndrome (LS). MMR gene testing for suspected mutation carriers is a reliable method to identify the mutation types and to discover mutation carriers. Given that carriers of MMR germline mutations have a hi...
Source: Hereditary Cancer in Clinical Practice - May 1, 2021 Category: Cancer & Oncology Source Type: research

CD36 polymorphisms and the age of disease onset in patients with pathogenic variants within the mutation cluster region of APC
ConclusionsThis study supports and strengthens our previous findings concerning CD36 and an association with disease onset in FAP, AFAP and FAP-MCR affected individuals. Knowledge about the role CD36 in adenoma development may provide greater insight into the development of colorectal cancer. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - April 29, 2021 Category: Cancer & Oncology Source Type: research

Impact of national guidelines on use of BRCA1/2 germline testing, risk management advice given to women with pathogenic BRCA1/2 variants and uptake of advice
ConclusionsGuidelines did not change the percentages of tested patients meeting genetic testing criteria but improved documentation of risk management advice by health professionals. Effective approaches to enhance compliance with guidelines are needed to improve risk management and quality of care. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - April 9, 2021 Category: Cancer & Oncology Source Type: research

Massive parallel sequencing in a family with rectal cancer
ConclusionBy massive parallel sequencing in a family suspected of carrying a highly penetrant rectal cancer predisposing genetic variant, we found six genetic missense variants with a potential connection to the rectal cancer in this family. One of them could be a high-risk genetic variant, or one or more of them could be low risk variants. The p.(Glu438Lys) variant in theCENPB gene was found to be of particular interest. The CENPB protein binds DNA and helps form centromeres during mitosis. It is involved in the WNT signaling pathway, which is critical for colorectal cancer development and its role in inherited rectal can...
Source: Hereditary Cancer in Clinical Practice - April 7, 2021 Category: Cancer & Oncology Source Type: research

Should the BCRA1/2-mutations healthy carriers be valid candidates for hematopoietic stem cell donation?
AbstractIt ’s still not clear whether the mutational status of BRCA-mutated healthy hematopoietic stem cells (HSCs) donors could have an impact on the engraftment. Comparing the studies present in literature, we focused on the correlation between BRCA mutations and the development of hematological malignanci es and Fanconi anemia (FA); then, we explored HSCs types, frequencies, and functions in the presence of BRCA mutations, as well as the reconstitution of hematopoiesis after chemotherapy and radiation treatments. The role of BRCA mutations in the FA showed a possible involvement in the onset of the d isease; the m...
Source: Hereditary Cancer in Clinical Practice - April 1, 2021 Category: Cancer & Oncology Source Type: research

CDKN2A germline alterations and the relevance of genotype-phenotype associations in cancer predisposition
AbstractAlthoughCDKN2A is well-known as a susceptibility gene for melanoma and pancreatic cancer, germline variants have also been anecdotally associated with a broader range of neoplasms including neural system tumors, head and neck squamous cell carcinomas, breast carcinomas, as well as sarcomas. TheCDKN2A gene encodes for two distinct tumor suppressor proteins, p16INK4A and p14ARF, however, the independent association of germline alterations affecting these two proteins with cancer is under-appreciated. Here, we reviewedCDKN2A germline alterations reported among individuals and families with cancer in the literature, sp...
Source: Hereditary Cancer in Clinical Practice - March 25, 2021 Category: Cancer & Oncology Source Type: research

Clinical implementation of an oncology ‐specific family health history risk assessment tool
Conclusions65  % of patients attending breast cancer clinics in this study are at-risk for hereditary conditions based on current guidelines. Using a patient-facing risk assessment platform enhances the ability to identify these patients systematically and with widespread acceptability and recognized value by p atients. As only a third of at-risk participants received referrals for genetic counseling, further understanding barriers to referral is needed to optimize hereditary risk assessment in oncology practices.Trial RegistrationNIH Clinical Trials registry,NCT04639934. Registered Nov 23, 2020 -- Retrospectively r...
Source: Hereditary Cancer in Clinical Practice - March 20, 2021 Category: Cancer & Oncology Source Type: research

Assessment of genetic referrals and outcomes for women with triple negative breast cancer in regional cancer centres in Australia
ConclusionsReferral pathways for women diagnosed with TNBC to cancer genetics services are performing well across our cancer centres. We identified a group of women who did not meet eligibility criteria for referral at their time of diagnosis, but would now be eligible, as guidelines have changed. The use of cross-discipline retrospective data reviews is a useful tool to identify patients who could benefit from being re-contacted over time for an updated cancer genetics assessment. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - February 26, 2021 Category: Cancer & Oncology Source Type: research

Room for improvement: One third of Lynch syndrome patients presenting for genetic testing in a highly specialised centre in Stockholm already have cancer
ConclusionA high proportion of patients (29%) were identified with Lynch syndrome after they had been diagnosed with an associated cancer, which suggests that there is significant room for improvement in the diagnosis of patients with Lynch syndrome before cancer develops. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - February 12, 2021 Category: Cancer & Oncology Source Type: research

Characteristics of BRCA1/2 pathogenic germline mutations in chinese NSCLC patients and a comparison with HBOC
AbstractBackground and purposesThe pathogenic BRCA1/2 germline mutations contributed to Hereditary Breast and Ovarian Cancer (HBOC) susceptibility. The features of BRCA1/2 germline mutations in non-small cell lung cancer (NSCLC) have not been systematically studied. Here we performed the first study investigating the characteristics of pathogenic BRCA1/2 germline mutations in Chinese NSCLC patients and compared them with those from Chinese HBOC.MethodsInformation on BRCA1/2 germline mutations from 9010 Chinese NSCLC patients were collected from available studies and analyzed, and compared with the BRCA1/2 germline mutation...
Source: Hereditary Cancer in Clinical Practice - February 9, 2021 Category: Cancer & Oncology Source Type: research

Risk of hematological malignancies in the families of patients treated for nodular lymphocyte-predominant Hodgkin lymphoma
ConclusionFHM is frequent in NLPHL. This study provided us many important insights for planning future studies in terms of interviewing technique, time, and resource allocation and genetic testing. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - February 9, 2021 Category: Cancer & Oncology Source Type: research

Clinical challenges in interpreting multiple pathogenic mutations in single patients
ConclusionsOngoing investigation is needed to improve our understanding of inherited susceptibility to disease in general and cancer predisposition syndromes, as this information has the potential to lead to the development of more precise and patient-specific counseling and surveillance strategies. The real-world adoption of new or improved technologies into clinical practice frequently requires medical decision-making in the absence of established understanding of gene-gene interactions. In the meantime, practitioners must be prepared to apply a rationale based on currently available knowledge to clinical decision-making...
Source: Hereditary Cancer in Clinical Practice - February 4, 2021 Category: Cancer & Oncology Source Type: research

Neoadjuvant therapy of BRCA1-driven ovarian cancer by combination of cisplatin, mitomycin C and doxorubicin
ConclusionsThe attempt to intensify NACT by administering combination of 3 drugs did not result in high rate of complete pathologic responses. However, there was a trend towards higher efficacy of the MAP regimen versus conventional TCbP scheme with regard to CRS and clinical outcomes. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - February 3, 2021 Category: Cancer & Oncology Source Type: research

BRCA1 and BRCA2 mutations in ovarian cancer patients from Belarus: update
ConclusionsThe frequency of 13 causativeBRCA1 andBRCA2 founder mutations in West Belarus was higher than in other Slavic countries. Testing ofBRCA1 (c.5266dupC, c.4035delA, c.3756_3759delGTCT, c.68_69delAG, c.1687C  >  T as well as c.181 T >  G) andBRCA2 (c.658_659delGT) mutations should be considered an inexpensive and sensitive test panel for this population. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - January 21, 2021 Category: Cancer & Oncology Source Type: research

A rare large duplication of MLH1 identified in Lynch syndrome
ConclusionsWe identified altogether three pathogenic/likely pathogenic variants in the MMR genes in three of the 19 sequenced families. TheMLH1 variants, a duplication of exons 4 to 13 and a frameshift variant, were novel, based on the InSiGHT and ClinVar databases; theMSH2 splice site variant was reported by a single submitter in ClinVar. As a variant class, duplications have rarely been reported in the MMR gene literature, particularly those covering several exons. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - January 19, 2021 Category: Cancer & Oncology Source Type: research

Recontacting non-BRCA1/2 breast cancer patients for germline CHEK2 c.1100del pathogenic variant testing: uptake and patient experiences
ConclusionsThe uptake (70%) of our approach was considered satisfactory. Patients considered the benefits more important than the psychosocial burden. Given the rapid developments in DNA-diagnostics, our findings may support future initiatives to recontact patients about additional genetic testing when they previously tested negative for a pathogenic variant in a breast cancer gene. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - January 19, 2021 Category: Cancer & Oncology Source Type: research

Novel PHOX2B germline mutation in childhood medulloblastoma: a case report
ConclusionsThis case revealed a de novoPHOX2B germline mutation as a potential cause of medulloblastoma in a child and suggests familial germline variant screening is useful when an affected family is considering having a second child. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - January 19, 2021 Category: Cancer & Oncology Source Type: research

A novel frequent BRCA1 recurrent variant c.5117G & gt; A (p.Gly1206Glu) identified after 20  years of BRCA1/2 research in the Baltic region: cohort study and literature review
ConclusionsBy combining three studies by our group of the same cohort in Latvia, frequency of theBRCA1/2 PV for unselected breast and ovarian cancer cases is 241/5060 (4.8%) and 162/1067 (15.2%) respectively. The frequency of three “historical” founder PV is up to 87.0% (369/424). Other non-founder PV contribute to at least 13.0% (55/424) and this proportion probably will rise by increasing numbers of theBRCA1/2 sequencing. In relative numbers, c.5117G  >  A is currently the third most frequent PV of theBRCA1 in population of Latvia, overcoming previously known third most common founder variant...
Source: Hereditary Cancer in Clinical Practice - January 19, 2021 Category: Cancer & Oncology Source Type: research

Advanced adenomas may be a red flag for hereditary cancer syndromes
Conclusions5% of patients with advanced adenomas in our retrospective series had a pathogenic germline mutation in a cancer predisposition gene. Though the patient with a pathogenic mutation inMLH1 met current clinical criteria for genetic testing, this was not recognized prior to referral; he was referred based on a personal history of advanced adenoma. Advanced polyps may be a red flag to identify patients who are at risk for hereditary cancer syndromes. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - January 12, 2021 Category: Cancer & Oncology Source Type: research

Heterogeneous constitutional mismatch repair deficiency with MSH6 missense mutation clinically benefits from pembrolizumab and regorafenib combination therapy: a case report and literature review
ConclusionOur case reported a CMMRD patient with heterogeneous MMR results who showed complicated response to ICIs, highlighting the importance of accurate diagnosis using targeted sequencing with multiple specimens to reveal the possible mechanism of response to ICI in patients with CMMRD. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - January 9, 2021 Category: Cancer & Oncology Source Type: research

Recurrent PALB2 mutations and the risk of cancers of bladder or kidney in Polish population
ConclusionWe found no difference in the prevalence of recurrentPALB2 mutations between cases and healthy controls. The mutations inPALB2 gene seem not to play a major role in bladder and kidney cancer development in Polish patients. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - January 8, 2021 Category: Cancer & Oncology Source Type: research

Familial pancreatic cancer with PALB2 and NBN pathogenic variants: a case report
ConclusionsFurther studies are required to develop strategies for managing FPCs to facilitate prompt diagnosis before their progression. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - January 7, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Prevalence of RECQL germline variants in Pakistani early-onset and familial breast cancer patients
An amendment to this paper has been published and can be accessed via the original article. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - January 7, 2021 Category: Cancer & Oncology Source Type: research

Revisiting multiple erroneous genetic testing results and clinical misinterpretations in a patient with Li-Fraumeni syndrome: lessons for translational medicine
ConclusionWe provide point-by-point discussion, reviewing multiple laboratory mistakes and clinical misinterpretations occurred with this patient. This case report exemplifies the need to involve rigorous clinical expertise in the daily practice of medical laboratory facilities. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - January 6, 2021 Category: Cancer & Oncology Source Type: research

Synchronous choroid plexus papilloma and Wilms tumor in a girl, disclosing a Li-Fraumeni syndrome
ConclusionsLFS has been associated with Choroid plexus carcinoma (CPC), but rarely with CPP as in our patient. That suggests that it may be advisable to consider the possibility of analyzing TP53 mutation, not only in all patients with CPC, but also in some patients with CPP, especially when histological or clinical evidences point out to perform this study. The dissimilar presentation of LFS among our patient ’s father, not having so far any neoplasia diagnosed, while her daughter presented precociously with two simultaneous different tumors, could be related to possible effects of modifier genes on the underlying m...
Source: Hereditary Cancer in Clinical Practice - January 6, 2021 Category: Cancer & Oncology Source Type: research

Metaplastic carcinoma of the breast and BRCA1 germline mutation: a case report and review
ConclusionsThere have been only 6 cases of metaplastic breast carcinoma with germlineBRCA1 mutations including our case. Patients withBRCA1 mutations may develop basal-like subtypes or M type of triple-negative breast cancer besides metaplastic breast cancers. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - January 6, 2021 Category: Cancer & Oncology Source Type: research

Prevalence of RECQL germline variants in Pakistani early-onset and familial breast cancer patients
ConclusionsOur data suggest that theRECQL gene plays a negligible role in breast cancer predisposition in Pakistan. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - December 20, 2020 Category: Cancer & Oncology Source Type: research

Characteristics and genetic testing outcomes of patients with clinically suspected paraganglioma/pheochromocytoma (PGL/PCC) syndrome in Singapore
ConclusionHereditary PGL/PCC accounts for only 0.6% of patients seen in an adult cancer genetics clinic in Asia.SDHD andSDHB genes remain the most important causative genes of hereditary PGL/PCC in Asia even when patients are tested with multi-gene NGS panel. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - December 11, 2020 Category: Cancer & Oncology Source Type: research

Metachronous cutaneous squamous cell carcinoma in a young patient as the only presenting symptom to uncover Lynch syndrome with MLH1 Germline mutation
ConclusionsCutaneous squamous cell carcinoma, although rare, can be the initial presenting symptom in patients with Lynch syndrome. This association has been described in patients with germline mutations in MLH1. Lynch syndrome should be considered when evaluating young patients presenting with recurrent cutaneous squamous cell carcinoma with positive family history of malignancy and/ or without any identifiable risk factors for skin cancers, including those with a durable and rapid response to immunotherapy. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - November 16, 2020 Category: Cancer & Oncology Source Type: research

An in-depth exploration of the post-test informational needs of BRCA1 and BRCA2 pathogenic variant carriers in Asia
This study aims to explore the informational needs ofBRCA1/2 pathogenic variant carriers in Asia to inform for the design of educational materials to support risk management decision-making.MethodsSemi-structured in-depth interviews were conducted with two male and 22 female English-speakingBRCA1/2 pathogenic variant carriers, aged 29 –66 years, identified through the Cancer Genetics Service at the National Cancer Centre Singapore. A grounded theory approach with thematic analysis was undertaken to extract dominant themes.ResultsFour themes were identified: (i) proactive online information seeking behaviors (i...
Source: Hereditary Cancer in Clinical Practice - October 23, 2020 Category: Cancer & Oncology Source Type: research

Biological and clinical impact of central nervous system hemangioblastomas in Chinese patients with von Hippel-Lindau disease: implications for treatment
AbstractObjectiveCentral nervous system (CNS) hemangioblastomas (HGBs) are the most frequent cause of mortality in patients with von Hippel-Lindau (VHL) genetic syndrome. However, there is a lack of large studies on the clinical features and optimal management of HGBs in Chinese patients.MethodsVHL-related HGB cases treated surgically at our hospital from 2012 to 2019 were evaluated. Patients and family members meeting the clinical diagnostic criteria underwent genetic testing. Clinical, genetic and relevant imaging data were analyzed.ResultsEighty-five VHL patients from 34 pedigrees in 16 Chinese provinces who underwent 1...
Source: Hereditary Cancer in Clinical Practice - October 22, 2020 Category: Cancer & Oncology Source Type: research

Preferences for breast cancer prevention among women with a BRCA1 or BRCA2 mutation
ConclusionsWomen revealed a willingness to undergo surgeries to achieve largest reduction in breast cancer risk, although this would not be recommended for a younger woman in her 20s. The goal of achieving the highest degree of cancer risk reduction is the primary driver for women withBRCA1 orBRCA2 mutations in selecting an intervention and a sequence of interventions, regardless of whether it is non-surgical or surgical. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - September 28, 2020 Category: Cancer & Oncology 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

Public support for healthcare-mediated disclosure of hereditary cancer risk information: Results from a population-based survey in Sweden
ConclusionsIn this study a majority of respondents wanted to be informed about a potential hereditary risk of CRC and preferred healthcare professionals to communicate this information. The two presented levels of CRC lifetime risk did not significantly affect the interest in being informed. Our data offer insights into the needs and preferences of the Swedish population, providing a rationale for developing complementary healthcare-assisted communication pathways to realise the full potential of targeted prevention of hereditary CRC. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - September 14, 2020 Category: Cancer & Oncology Source Type: research

Retrospective review of outcomes in patients with DNA-damage repair related pancreatic cancer
ConclusionsHistorical survival in patients with advanced and metastatic pancreas cancer is poor. Results of this DDR-subset of patients do show significantly superior outcomes, likely secondary to exposure to platinum drugs. This data, alongside other similar cohorts, would favor the DDR-genes being a predictive marker with improved survival if exposed to these drugs and the new class of drugs, PARP-inhibitors. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - August 9, 2020 Category: Cancer & Oncology Source Type: research

Polymorphisms in MMP-1 , MMP-2 , MMP-7, MMP-13 and MT2A do not contribute to breast, lung and colon cancer risk in polish population
ConclusionsAnalyses of polymorphisms, rs1799750 inMMP-1, rs243865 inMMP-2, rs11568818 inMMP-7, rs2252070 inMMP-13 and rs28366003 inMT2A in relation to serum Zn level did not show significant association with breast, lung and colon cancer risk among polish patients. Further studies are needed to verify this observation. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - July 30, 2020 Category: Cancer & Oncology Source Type: research

Informing patients about their mutation tests: CDKN2A c.256G & gt;A in melanoma as an example
ConclusionsThe pedigree data showed at the most a low penetrance variant, which, if taken into consideration, might have altered the provided diagnosis. When dealing with ‘practically’ unknown variants the counselors would be advised to incorporate a detailed family history rather than basing predictions on functionality provided by sequencing facilities. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - July 30, 2020 Category: Cancer & Oncology Source Type: research

An American patient with polyposis carrying a Scandinavian AXIN2 pathogenic variant
(Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - July 29, 2020 Category: Cancer & Oncology Source Type: research

Adherence to National Comprehensive Cancer Network Guidelines for BRCA testing among high risk breast Cancer patients: a retrospective chart review study
ConclusionsAdherence to NCCNBRCA testing guidelines is high in this group of predominantly medical oncologists with extensive experience, with a high proportion having a genetic counselor in practice. Testing rates can be improved in patients with risk factors related to male relatives. High level of compliance to guidelines in a community setting is possible with a delivery model for genetic counseling and testing. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - June 5, 2020 Category: Cancer & Oncology Source Type: research

Increased risk for uterine cancer among first-degree relatives to Swedish gastric cancer patients
ConclusionsThere seems to be an increased risk of both gastric cancer and uterine cancer in the families of gastric cancer survivors, indicating a possible hereditary connection between these two cancer types. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - June 4, 2020 Category: Cancer & Oncology Source Type: research

Correction to: Expectations and psychological issues before genetic counseling: analysis of distress determinant factors
An amendment to this paper has been published and can be accessed via the original article. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - May 18, 2020 Category: Cancer & Oncology Source Type: research

Expectations and psychological issues before genetic counseling: analysis of distress determinant factors
ConclusionsGreater level of distress identified on females, single and younger subjects. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - April 28, 2020 Category: Cancer & Oncology Source Type: research

Development and validation of next generation sequencing based 35-gene hereditary cancer panel
ConclusionsThe use of targeted NGS-based multigene testing panels to provide comprehensive analysis of cancer susceptible genes has been considered a viable option. In the present study, we developed and validated a 35-gene panel for testing 8 common cancers using next-generation sequencing (NGS). The performance of our hereditary cancer panel is assessed across a board range of variants in the 35 genes to support clinical use. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - April 27, 2020 Category: Cancer & Oncology Source Type: research

A rare missense variant in APC interrupts splicing and causes AFAP in two Danish families
ConclusionsBased on functional and co-segregation data we classify theAPC c.289G>A, p.(Gly97Arg) variant as pathogenic (class 5). Our findings emphasize the importance of a functional evaluation of missense variants although located far from the exon-intron boundaries. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - April 6, 2020 Category: Cancer & Oncology Source Type: research

An interesting case of likely BRCA2 related bilateral breast cancer with metastasis in the fimbrial part of fallopian tube
ConclusionWe present an interesting and quite rare case of two primary breast carcinomas in a patient with a knownBRCA2 pathogenic variant with metastasis in the fimbrial part of the left Fallopian tube. We conclude that there were two primary breast tumours and the one from 2011 spread into the fimbrial part of the left Fallopian tube in 2016. Despite the fact that molecular analyses could not confirm the joint tumour origin, we believe that there was a receptor status conversion over time explaining different receptor status. The possibility of a triple-negative metastasis from the tumour treated in 1998 is less probable...
Source: Hereditary Cancer in Clinical Practice - March 18, 2020 Category: Cancer & Oncology Source Type: research

The Prospective Lynch Syndrome Database reports enable evidence-based personal precision health care
AbstractThe aims of the Prospective Lynch Syndrome Database (PLSD) are to provide empirical prospectively observed data on the incidences of cancer in different organs, survival following cancer and the effects of interventions in carriers of pathogenic variants of the mismatch repair genes (path_MMR) categorized by age, gene and gender. Although PLSD is assumption-free, as with any study the ascertainment procedures used to identify the study cohort will introduce selection biases which have to be declared and considered in detail in order to provide robust and valid results. This paper provides a commentary on the method...
Source: Hereditary Cancer in Clinical Practice - March 13, 2020 Category: Cancer & Oncology Source Type: research

Diet, weight management, physical activity and Ovarian & amp; Breast Cancer Risk in women with BRCA1/2 pathogenic Germline gene variants: systematic review
ConclusionsThere is not enough evidence to suggest tailored recommendations for dietary habits or weight management among women withBRCA1/2 pathogenic variants compared to the general population for ovarian and breast cancer risk-reduction, and physical activity recommendations should remain the same. (Source: Hereditary Cancer in Clinical Practice)
Source: Hereditary Cancer in Clinical Practice - March 6, 2020 Category: Cancer & Oncology Source Type: research

Ubiquitous neurocognitive dysfunction in familial adenomatous polyposis: proof-of-concept of the role of APC protein in neurocognitive function
AbstractBackgroundFamilial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by germline mutations in the APC gene. Patients with FAP have multiple extraintestinal manifestations that follow a genotype-phenotype pattern; however, few data exist characterizing their cognitive abilities. Given the role of the APC protein in development of the central nervous system, we hypothesized that patients with FAP would show differences in cognitive functioning compared to controls.MethodsMatched case-control study designed to evaluate cognitive function using the Test of Nonverbal Intelligence-4, the Bateria III Wo...
Source: Hereditary Cancer in Clinical Practice - February 23, 2020 Category: Cancer & Oncology Source Type: research