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
Barriers to completion of cascade genetic testing: how can we improve the uptake of testing for hereditary breast and ovarian cancer syndrome?
AbstractCascade testing for familial cancer syndromes has historically been difficult to execute. As part of a facilitated cascade testing pathway, we evaluated barriers to completion of cascade testing. Our previously published study evaluated a facilitated cascade testing pathway whereby a genetics team facilitated at-risk relative (ARR) cascade testing through telephone genetic counseling and mailed saliva kit testing. This follow-up study evaluated barriers to completion of cascade genetic testing through six-month follow-up telephone interviews. Probands identified 114 ARRs, of whom 97 were successfully contacted by t...
Source: Familial Cancer - October 8, 2022 Category: Cancer & Oncology Source Type: research
Determinants of adherence to recommendations on physical activity, red and processed meat intake, and body weight among lynch syndrome patients
This study aimed to identify determinants of adherence to lifestyle and body weight recommendations for cancer prevention among Lynch Syndrome (LS) patients. Cross-sectional baseline data of LS patients participating in the Lifestyle& Lynch (LiLy) study was used to assess determinants of adherence to the World Cancer Research Fund cancer prevention recommendations on body weight, physical activity, and red and processed meat intake. Adherence and potential determinants of adherence were assessed using questionnaires. Multivariable logistic regression analyses were conducted to identify determinants of adherence. Of the...
Source: Familial Cancer - September 24, 2022 Category: Cancer & Oncology Source Type: research
Identifying the BRCA1 c.-107A & gt; T variant in Dutch patients with a tumor BRCA1 promoter hypermethylation
AbstractAn inherited single nucleotide variant (SNV) in the 5 ′UTR of theBRCA1 gene c.-107A > T was identified to be related toBRCA1 promoter hypermethylation and a hereditary breast and ovarian cancer phenotype in two UK families. We investigated whether thisBRCA1 variant was also present in a Dutch cohort of breast and ovarian cancer patients with tumorBRCA1 promoter hypermethylation. We selected all breast and ovarian cancer cases that tested positive for tumorBRCA1 promoter hypermethylation at the Netherlands Cancer Institute and Sanger sequenced the specific mutation in the tumor DNA. In total, we identif...
Source: Familial Cancer - September 16, 2022 Category: Cancer & Oncology Source Type: research
A pilot study investigating feasibility of mainstreaming germline BRCA1 and BRCA2 testing in high-risk patients with breast and/or ovarian cancer in three tertiary Cancer Centres in Ireland
AbstractIn the Republic of Ireland (ROI),BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient’s BRCA status. “Mainstreaming”BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the...
Source: Familial Cancer - August 27, 2022 Category: Cancer & Oncology Source Type: research
Disclosure of genetic risk to dating partners among young adults with von Hippel-Lindau disease
This study assessed young adults ’ attitudes towards dating and decisions related to disclosing a diagnosis of VHL to a dating partner. Twenty-six young adults with VHL participated in semi-structured interviews exploring this issue, using a guide informed by the literature in consultation with providers and an individual with VH L. Interviews were coded with a primarily deductive approach using codes derived from the literature, with inductive coding employed for perspectives unique to VHL. Our results support previous findings that genetic disease contributes to fear of rejection due to decreased desirability. However,...
Source: Familial Cancer - August 19, 2022 Category: Cancer & Oncology Source Type: research
Endoscopic management of familial adenomatous polyposis targeting colorectal lesions greater than 5 mm in size: a single-center retrospective study
This study examined our endoscopic management and prognostic results for patients with familial adenomatous polyposis who refused to undergo colectomy. We retrospectively analyzed the data of 12 patients with familial adenomatous polyposis treated at our hospital between January 1995 and December 2020. All patients opted to postpone prophylactic colectomy although they had significant polyp burdens and underwent endoscopic management, in which colorectal polyps sized > 5 mm were thoroughly resected during baseline colonoscopies and subsequently, newly arising colorectal polyps sized > 5 mm were periodica...
Source: Familial Cancer - August 5, 2022 Category: Cancer & Oncology Source Type: research
Analysis of uveal melanomas and paired constitutional DNA for exclusion of a BAP1-tumor predisposition syndrome
AbstractUveal melanoma (UM) is a rare tumor originating from melanocytic cells in the eye. Familial aggregation of UM is rare and can occur as part of the tumor predisposition syndrome BAP1-TPDS. However, family history alone will only identify a subset of patients with BAP1-TPDS. In the present study, we used sequential testing of tumor and blood DNA from UM patients for differential diagnosis of BAP1-TPDS. The study group was an unselected prospective cohort of patients from whom UM tissue was available. First, chromosome 3 status in tumor DNA was determined in all 140 patients who consented to participate. As tumors wit...
Source: Familial Cancer - August 3, 2022 Category: Cancer & Oncology Source Type: research
