Immune escape and resistance to immunotherapy in mismatch repair deficient tumors
Up to 30% of colorectal, endometrial and gastric cancers have a deficiency in mismatch repair (MMR) protein expression due to either germline or epigenetic inactivation. Patients with Lynch Syndrome who inherit an inactive MMR allele have an up to 80% risk for developing a mismatch repair deficient (MMRd) cancer. Due to an inability to repair DNA, MMRd tumors present with genomic instability in microsatellite regions (MS). Tumors with high MS instability (MSI-H) are characterized by an increased frequency of insertion/deletions (indels) that can encode novel neoantigens if they occur in coding regions. The high tumor antig...
Source: Frontiers in Immunology - July 10, 2023 Category: Allergy & Immunology Source Type: research
Recurrent papillary bladder tumors in a boy with Lynch syndrome
Lynch syndrome (LS) is an autosomal dominant genetic disorder defined by germline mutations in one of four mismatch repair (MMR) genes including PMS2, MLH2, MSH1, MSH2 or deletion in the EPCAM gene. [1] The most common urologic manifestation of LS is upper tract urothelial carcinoma (UTUC), which occurs in up to 20% of patients with LS. [2] While data are scarce, there is growing evidence of an increased relative risk of bladder malignancy in patients with LS. [3, 4] Bladder tumors in children are a rare entity and the link between pediatric bladder tumors and LS has not been previously reported to our knowledge. (Source: Urology)
Source: Urology - July 5, 2023 Category: Urology & Nephrology Authors: Rafael Tua-Caraccia, Austin Livingston, Jonathan C. Routh Source Type: research
Mutational pattern off homologous recombination repair (HRR) ‐related genes in upper tract urothelial carcinoma
ConclusionsOur results imply that the detection of HRR gene mutations can predict recurrence in patients with UC. In addition, this study provides a path to explore the role of HRR-directed therapies, including PARPis, chemotherapy, and immunotherapy. (Source: Cancer Medicine)
Source: Cancer Medicine - June 30, 2023 Category: Cancer & Oncology Authors: Kaiwei Yang,
Wei Yu,
Huanhuan Liu,
Feng Lou,
Shanbo Cao,
Huina Wang,
Zhisong He Tags: RESEARCH ARTICLE Source Type: research
Dietary behaviours of individuals with Lynch syndrome at high risk of colorectal cancer: results from the AAS-Lynch study
Individuals with Lynch syndrome (LS) have a high lifetime risk of developing colorectal cancer (CRC) due to genetic alterations. Nutrition is one of the main modifiable risk factors for sporadic CRC, however this has not been established in LS patients. The present study aimed to give a detailed overview of dietary intakes in individuals with LS, and associated individual characteristics. (Source: Clinical Nutrition ESPEN)
Source: Clinical Nutrition ESPEN - June 30, 2023 Category: Nutrition Authors: No émie Demaré, Chantal Julia, Alice Bellicha, Mourad Benallaoua, Amal Ait Omar, Nathalie Arnault, Robert Benamouzig, Mélanie Deschasaux-Tanguy, AAS-Lynch study group 2022 Tags: Original article Source Type: research
From variant of unknown significance to likely pathogenic: Characterization and pathogenicity determination of a large genomic deletion in the MLH1 gene
ConclusionOur finding suggested that although NGS technologies have increased variant detection yield, combined approaches were still needed for complex variant characterization and pathogenicity assessment. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - June 23, 2023 Category: Genetics & Stem Cells Authors: Ahmed Bouras,
Clementine Legrand,
Jihen Kourda,
Eric Ruano,
Chlo é Grand‐Masson,
Cedrick Lefol,
Qing Wang Tags: CLINICAL REPORT Source Type: research
From variant of unknown significance to likely pathogenic: Characterization and pathogenicity determination of a large genomic deletion in the MLH1 gene
CONCLUSION: Our finding suggested that although NGS technologies have increased variant detection yield, combined approaches were still needed for complex variant characterization and pathogenicity assessment.PMID:37350751 | DOI:10.1002/mgg3.2231 (Source: Molecular Medicine)
Source: Molecular Medicine - June 23, 2023 Category: Molecular Biology Authors: Ahmed Bouras Clementine Legrand Jihen Kourda Eric Ruano Chlo é Grand-Masson Cedrick Lefol Qing Wang Source Type: research
Cancer surveillance for transgender and gender diverse patients with Lynch syndrome: a practice resource of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer
AbstractTransgender and gender diverse (TGD) populations with hereditary cancer syndromes face unique obstacles to identifying and obtaining appropriate cancer surveillance and risk-reducing procedures. There is a lack of care provider knowledge about TGD health management. Lynch syndrome (LS) is one of the most common hereditary cancer syndromes, affecting an estimated 1 in 279 individuals. There are no clinical guidelines specific for TGD individuals with LS, highlighting a need to improve the quality of care for this population. There is an urgent need for cancer surveillance recommendations for TGD patients. This comme...
Source: Familial Cancer - June 21, 2023 Category: Cancer & Oncology Source Type: research
Lung Cancer in Patients With Lynch Syndrome: Association or Coincidence?
Clin Lung Cancer. 2023 May 31:S1525-7304(23)00109-2. doi: 10.1016/j.cllc.2023.05.007. Online ahead of print.ABSTRACTLynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC) occurs due to microsatellite instability (MSI) caused by mutations in one of the mismatch repair genes leading to deficient mismatch repair proteins (dMMR). Although lung cancer is very common there is no established association between LS and lung cancer. In this manuscript we describe a case of lung cancer in a LS patient and then summarize available literature on this topic. Sixty seven y/o female patient with history of s...
Source: Clinical Lung Cancer - June 19, 2023 Category: Cancer & Oncology Authors: Umair Majeed Karan Seegobin Jason Lewis Shenduo Li Yujie Zhao Yanyan Lou Rami Manochakian Source Type: research
Lung Cancer in Patients With Lynch Syndrome: Association or Coincidence?
Clin Lung Cancer. 2023 May 31:S1525-7304(23)00109-2. doi: 10.1016/j.cllc.2023.05.007. Online ahead of print.ABSTRACTLynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC) occurs due to microsatellite instability (MSI) caused by mutations in one of the mismatch repair genes leading to deficient mismatch repair proteins (dMMR). Although lung cancer is very common there is no established association between LS and lung cancer. In this manuscript we describe a case of lung cancer in a LS patient and then summarize available literature on this topic. Sixty seven y/o female patient with history of s...
Source: Clinical Colorectal Cancer - June 19, 2023 Category: Cancer & Oncology Authors: Umair Majeed Karan Seegobin Jason Lewis Shenduo Li Yujie Zhao Yanyan Lou Rami Manochakian Source Type: research
Prognostic value of Lynch syndrome, BRAFV600E, and RAS mutational status in dMMR/MSI ‐H metastatic colorectal cancer in a pooled analysis of Dutch and French cohorts
ConclusionBRAFV600E andRAS mutational status are not associated with prognosis in dMMR mCRC patients, in contrast to pMMR mCRC patients. Lynch syndrome is also not an independent prognostic factor for survival. These findings underline that prognostic factors of patients with dMMR mCRC are different of those with pMMR, which could be taken into consideration when prognosis is used for clinical decision-making in dMMR mCRC patients and underline the complex heterogeneity of mCRC. (Source: Cancer Medicine)
Source: Cancer Medicine - June 16, 2023 Category: Cancer & Oncology Authors: Koen Zwart,
Frederieke H. Baan,
Romain Cohen,
Thomas Aparicio,
Christelle Fouchardi ére,
Thierry Lecomte,
Cornelis J. A. Punt,
David Sefrioui,
Rik J. Verheijden,
Geraldine R. Vink,
G. Emerens Wensink,
Aziz Zaanan,
Miriam Koopman,
David Touge Tags: RESEARCH ARTICLE Source Type: research
Clinical Multigene Panel Testing Identifies Racial and Ethnic Differences in Germline Pathogenic Variants Among Patients With Early-Onset Colorectal Cancer
CONCLUSION: Germline genetic features differed by race/ethnicity in young patients with CRC, suggesting that current multigene panel tests may not be representative of EOCRC risk in diverse populations. Further study is needed to optimize genes selected for genetic testing in EOCRC via ancestry-specific gene and variant discovery to yield equitable clinical benefits for all patients and to mitigate inequities in disease burden.PMID:37319387 | DOI:10.1200/JCO.22.02378 (Source: Clinical Colorectal Cancer)
Source: Clinical Colorectal Cancer - June 15, 2023 Category: Cancer & Oncology Authors: Hannah M Seagle Samantha R Keller Sean V Tavtigian Carolyn Horton Andreana N Holowatyj Source Type: research
A mosaic pathogenic variant in MSH6 causes MSH6-deficient colorectal and endometrial cancer in a patient classified as suspected Lynch syndrome: a case report
This study highlights the utility of tumor sequencing to guide sensitive ddPCR testing to detect low-level mosaicism in the MMR genes. Further investigation of the prevalence of MMR mosaicism is needed to inform routine diagnostic approaches and genetic counselling. (Source: Familial Cancer)
Source: Familial Cancer - June 15, 2023 Category: Cancer & Oncology Source Type: research
Gut Microbiome Composition in Lynch Syndrome With and Without History of Colorectal Neoplasia and Non-Lynch Controls
ConclusionsDifferences in microbiome composition between LS and non-LS may suggest a microbiome pattern unique to LS formed by underlying differences in epithelial biology and immunology. We found specific taxa differences among LS groups, which may be due to underlying anatomy. Larger prospective studies following for CRN diagnosis and microbiome composition changes are needed to determine if microbiome composition contributes to CRN development in patients with LS. (Source: Journal of Gastrointestinal Cancer)
Source: Journal of Gastrointestinal Cancer - June 13, 2023 Category: Cancer & Oncology Source Type: research
Investigating the prevalence of pathogenic variants in Saudi Arabian patients with familial cancer using a multigene next generation sequencing panel
Oncotarget. 2023 Jun 12;14:580-594. doi: 10.18632/oncotarget.28457.ABSTRACTFamily history is an important factor in determining hereditary cancer risk for many cancer types. The emergence of next-generation sequencing (NGS) has expedited the discovery of many hereditary cancer susceptibility genes and the development of rapid, affordable testing kits. Here, a 30-gene targeted NGS panel for hereditary cancer risk assessment was tested and validated in a Saudi Arabian population. A total of 310 subjects were screened, including 57 non-cancer patients, 110 index patients with cancer and 143 of the cancer patients' family memb...
Source: Oncotarget - June 12, 2023 Category: Cancer & Oncology Authors: Musa AlHarbi Nahla Ali Mobark Wael Abdel Rahman AlJabarat Hadeel ElBardis Ebtehal AlSolme Abdullah Bany Hamdan Ali H AlFakeeh Fatimah AlMushawah Fawz AlHarthi Abdullah A AlSharm Ali Abdullah O Balbaid Naji AlJohani Alicia Y Zhou Heather A Robinson Saleh A Source Type: research
Investigating the prevalence of pathogenic variants in Saudi Arabian patients with familial cancer using a multigene next generation sequencing panel
Oncotarget. 2023 Jun 12;14:580-594. doi: 10.18632/oncotarget.28457.ABSTRACTFamily history is an important factor in determining hereditary cancer risk for many cancer types. The emergence of next-generation sequencing (NGS) has expedited the discovery of many hereditary cancer susceptibility genes and the development of rapid, affordable testing kits. Here, a 30-gene targeted NGS panel for hereditary cancer risk assessment was tested and validated in a Saudi Arabian population. A total of 310 subjects were screened, including 57 non-cancer patients, 110 index patients with cancer and 143 of the cancer patients' family memb...
Source: Oncotarget - June 12, 2023 Category: Cancer & Oncology Authors: Musa AlHarbi Nahla Ali Mobark Wael Abdel Rahman AlJabarat Hadeel ElBardis Ebtehal AlSolme Abdullah Bany Hamdan Ali H AlFakeeh Fatimah AlMushawah Fawz AlHarthi Abdullah A AlSharm Ali Abdullah O Balbaid Naji AlJohani Alicia Y Zhou Heather A Robinson Saleh A Source Type: research
