Perspectives on the implications of carrying putative pathogenic variants in the medulloblastoma predisposition genes ELP1 and GPR161
AbstractRecent genetic sequencing studies in large series ’ of predominantly childhood medulloblastoma have implicated loss-of-function, predominantly truncating, variants in theELP1 andGPR161 genes in causation of the MBSHH subtype specifically. The latter association, along with a report of an index case with some features of Gorlin syndrome has led to speculation thatGPR161 may also cause Gorlin syndrome. We show that these genes are associated with relatively low absolute risks of medulloblastoma from extrapolating lifetime risks in the general population and odds ratios from the population database gnomAD. The proje...
Source: Familial Cancer - March 24, 2023 Category: Cancer & Oncology Source Type: research
Hereditary acute myeloid leukemia associated with C-terminal CEBPA germline variants
AbstractAcute myeloid leukemia with germlineCEBPA mutation is a subtype of acute myeloid leukemia that is associated with a favorable prognosis. Most of the reported cases of acute myeloid leukemia withCEBPA germline variants involve a germline variant in the N-terminus and a somatic variant in the C-terminus. There are only a few reported cases where theCEBPA germline variant has been identified in the C-terminus and the somatic variant in the N-terminus. This case report and review of the literature illustrates that, although acute myeloid leukemia withCEBPA N- or C-terminal germline variants have certain similarities su...
Source: Familial Cancer - March 6, 2023 Category: Cancer & Oncology Source Type: research
Characteristics of familial pancreatic cancer families with additional colorectal carcinoma
AbstractFamilial pancreatic cancer (FPC) is a rare hereditary tumor entity with broad phenotypic heterogeneity, including colorectal carcinoma (CRC) in some families. The underlying factors for this co-occurrence are still not well evaluated. FPC families in the National Case Collection of Familial Pancreatic Cancer with an additional occurrence of CRC were analyzed regarding the phenotype, genotype and recommendation for a clinical screening program. The total cohort of 272 FPC families included 30 (11%) families with at least one CRC case. The proportion of affected family members with PDAC was 16.1% (73/451) compared to...
Source: Familial Cancer - January 31, 2023 Category: Cancer & Oncology Source Type: research
Heritable methylation marks associated with prostate cancer risk
AbstractDNA methylation marks that are inherited from parents to offspring are known to play a role in cancer risk and could explain part of the familial risk for cancer. We therefore conducted a genome-wide search for heritable methylation marks associated with prostate cancer risk. Peripheral blood DNA methylation was measured for 133 of the 469 members of 25 multiple-case prostate cancer families, using the EPIC array. We used these families to systematically search the genome for methylation marks with Mendelian patterns of inheritance, then we tested the 1,000 most heritable marks for association with prostate cancer ...
Source: Familial Cancer - January 28, 2023 Category: Cancer & Oncology Source Type: research
2022 CGA-IGC Annual Meeting: The collaborative group of the Americas on Inherited Gastrointestinal Cancer November 11 –13, 2022
(Source: Familial Cancer)
Source: Familial Cancer - January 23, 2023 Category: Cancer & Oncology Source Type: research
Evaluating the role of CHEK2 p.(Asp438Tyr) allele in inherited breast cancer predisposition
AbstractCHEK2 is a well-established breast cancer susceptibility gene. The most frequent pathogenicCHEK2 variant is 1100delC, a loss-of-function mutation conferring 2-fold risk for breast cancer. This gene also harbors other rare variants encountered in the clinical gene panels for hereditary cancer. One of these isCHEK2 c.1312 G > T, p.(Asp438Tyr) in the kinase domain of the protein, but due to its rarity its clinical significance for breast cancer predisposition has remained unclear. Here, we tested the prevalence ofCHEK2 p.(Asp438Tyr) allele showing enrichment in the Northern Finnish population, in a total of 2...
Source: Familial Cancer - January 19, 2023 Category: Cancer & Oncology Source Type: research
Pilot study of the prevalence of autoimmune disorders in Li-Fraumeni syndrome
(Source: Familial Cancer)
Source: Familial Cancer - January 11, 2023 Category: Cancer & Oncology Source Type: research
Two unique BAP1 pathogenic variants identified in the same family by panel cascade testing
AbstractGermline pathogenic variants in the tumor suppressor geneBAP1 are associated with the hereditary tumor predisposition syndrome with susceptibility to uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and other cancers. GermlineBAP1 pathogenic variants are rare in the non-cancer general population with an estimated carrier frequency of 1:19,898 but more common in cancer patients with a carrier frequency of 1:1299. In the following we present the first report of a family with two uniqueBAP1 pathogenic variants. Retrospective case report of a family with two unique pathogenic variants inBAP1. A m...
Source: Familial Cancer - December 14, 2022 Category: Cancer & Oncology Source Type: research
A PMS2 non-canonical splicing site variant leads to aberrant splicing in a patient suspected for lynch syndrome
In this report, we describe the analysis of such an intronic variant (c.251-5T > C) detected in an 82-year-old patient diagnosed with endometrial cancer displaying microsatellite instability and the loss of PMS2 expression displayed. RNA analysis demonstrated that this variant lead to the complete exon 4 skipping, resulting in the synthesis of a truncated protein. This findin g shows the relevance of functional RNA analysis in the non-canonical intronic variant assessment and the importance of systematic evaluation of MSI/loss of expression of MMR genes for LS screening in patients with endometrial cancers. (Source: Familial Cancer)
Source: Familial Cancer - November 29, 2022 Category: Cancer & Oncology Source Type: research
A retrospective cohort study of genetic referral and diagnosis of lynch syndrome in patients with cutaneous sebaceous lesions
AbstractImmunohistochemistry (IHC) of cutaneous sebaceous lesions (SL) can be used to screen patients for Lynch syndrome (LS). There is little data on rates of genetic referral and outcomes of genetic testing for patients with SL. This single-center retrospective study characterizes 400 + patients with SL, including IHC results, genetics referrals, and outcomes of genetic testing. Retrospective chart reviews were performed for patients with a pathology-confirmed diagnosis of SL at the University of Michigan between January 2009 and December 2019. 447 patients with 473 SL were identified. Excluding 20 patients with kno...
Source: Familial Cancer - November 28, 2022 Category: Cancer & Oncology Source Type: research
Characterization of sebaceous and non-sebaceous cutaneous manifestations in patients with lynch syndrome: a systematic review
AbstractA subset of patients with Lynch Syndrome demonstrates cutaneous manifestations of the disorder. Characterization of these Lynch-related skin lesions could help in early recognition of patients with Lynch Syndrome. A broad search of the literature on OVID Medline and Embase was carried out to capture papers reporting cutaneous manifestations in Lynch Syndrome patients. The results were uploaded into Mendeley reference management software. The PRISMA workflow was used in the literature selection process. In this systematic review, data were collected from 961 cases from 413 studies, including 380 molecularly confirme...
Source: Familial Cancer - November 23, 2022 Category: Cancer & Oncology Source Type: research
Laboratory variation in the grading of dysplasia of duodenal adenomas in familial adenomatous polyposis patients
AbstractTo prevent duodenal and ampullary cancer in familial adenomatous polyposis (FAP) patients, a diagnosis of high grade dysplasia (HGD) plays an important role in the clinical management. Previous research showed that FAP patients are both over- and undertreated after a misdiagnosis of HGD, indicating unwarranted variation. We aimed to investigate the laboratory variation in dysplasia grading of duodenal adenomas and explore possible explanations for this variation. We included data from all Dutch pathology laboratories between 1991 and 2020 by retrieving histology reports from upper endoscopy specimens of FAP patient...
Source: Familial Cancer - November 19, 2022 Category: Cancer & Oncology Source Type: research
Next-generation universal hereditary cancer screening: implementation of an automated hereditary cancer screening program for patients with advanced cancer undergoing tumor sequencing in a large HMO
AbstractVariants in hereditary cancer risk genes are frequently identified following tumor-based DNA sequencing and represent an opportunity to diagnose hereditary cancer. We implemented an automated hereditary cancer screening program in a large HMO for all patients who underwent tumor-based DNA sequencing to identify patients with hereditary cancer and determine if this approach augmented existing genetic counseling approaches driven by personal/family history criteria. Regular automated searches of a centralized tumor DNA variant database were performed for ATM, BRCA1, BRCA2, MLH1, MSH2, MSH6, PALB2, and/or PMS2 variant...
Source: Familial Cancer - October 20, 2022 Category: Cancer & Oncology Source Type: research
InSiGHT 2022 Abstract Publishing and Best Abstract Awards
(Source: Familial Cancer)
Source: Familial Cancer - October 19, 2022 Category: Cancer & Oncology Source Type: research
A need to tailor surveillance based on family history: describing a highly penetrant familial paraganglioma kindred with an SDHD pathogenic variant
This study aims to characterize a multi-generational family withSDHD p.Trp43* PVs and potential genotype –phenotype considerations for surveillance. Individuals with a paternally inheritedSDHD p.Trp43*(c.129G > A) PV were identified. Genetic, medical and family histories were abstracted, including clinical characteristics, tumor histories, and treatment approaches. Eleven individuals with theSDHD PV in the same kindred were diagnosed with 41SDHx-related tumors across all family members. Eight individuals developed 27 head and neck PGL of varying origins, and seven individuals developed tumors outside of the head...
Source: Familial Cancer - October 12, 2022 Category: Cancer & Oncology Source Type: research
