Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients
In this study, we investigated 80 unexplained colorectal polyposis patients without germline pathogenic variants in known polyposis predisposing genes to detect mosaic and deep intronicAPC variants. All patients developed more than 50 colorectal polyps, with adenomas being predominantly observed. To detectAPC mosaicism, we performed next-generation sequencing (NGS) in leukocyte DNA. Furthermore, using Sanger sequencing, the cohort was screened for the following previously reported deep intronic pathogenic germlineAPC variants: c.1408 + 731C > T, p.(Gly471Serfs*55), c.1408 + 735A > T, p.(Gly471Serfs...
Source: Familial Cancer - March 8, 2021 Category: Cancer & Oncology Source Type: research
Effective identification of cancer predisposition syndromes in children with cancer employing a questionnaire
Conclusion: The CPS questionnaire appears to significantly improve the diagnosis of children with CPS among children with a newly diagnosed oncologic condition. (Source: Familial Cancer)
Source: Familial Cancer - March 2, 2021 Category: Cancer & Oncology Source Type: research
Proportion of children with cancer that have an indication for genetic counseling and testing based on the cancer type irrespective of other features
Abstract In children with cancer, specific clinical features such as physical anomalies, occurrence of cancer in young relatives, specific cancer histologies, and unique mutation/methylation signatures may indicate the presence of an underlying cancer predisposition syndrome (CPS). The proportion of children with a cancer type suggesting a CPS among all children with cancer is unknown. To determine the proportion of children with cancer types suggesting an underlying CPS among children with cancer. We evaluated the number of children with cancer types strongly associated with CPS diagnosed in Germany between 2007 and 2016....
Source: Familial Cancer - February 26, 2021 Category: Cancer & Oncology Source Type: research
Managing gastric cancer risk in lynch syndrome: controversies and recommendations
(Source: Familial Cancer)
Source: Familial Cancer - February 21, 2021 Category: Cancer & Oncology Source Type: research
The needs of Southeast Asian BRCA mutation carriers considering risk-reducing salpingo-oophorectomy: a qualitative study
This study aimed to explore the decision-making needs of Malaysian BRCA mutation carriers as an exemplar for the Southeast Asian community. In-depth interviews and clinic observations were conducted with 31 BRCA mutation carriers and analysed thematically. The core theme identified was ‘Coping with complex information and alleviating uncertainties’ with the following subthemes: (1) the need for an adjustment period, (2) information support, (3) social support and, (4) religious support. We found that women required time to accept their BRCA mutation status before they were rea dy to make a risk-reducing choice; that un...
Source: Familial Cancer - February 19, 2021 Category: Cancer & Oncology Source Type: research
Choose and stay on one out of two paths: distinction between clinical versus research genetic testing to identify cancer predisposition syndromes among patients with cancer
(Source: Familial Cancer)
Source: Familial Cancer - February 12, 2021 Category: Cancer & Oncology Source Type: research
Approach to screening for Familial Adenomatous Polyposis (FAP) in a cohort of 226 patients with Desmoid-type Fibromatosis (DF): experience of a specialist center in the UK
ConclusionsCTNNB1 ± APC testing and colonoscopy are useful tools for the screening of patients with DF.CTNNB1 molecular testing should be performed in all cases of newly diagnosed DF. NegativeCTNNB1 results, alongside clinical assessment, should promptAPC testing and/or colonoscopy. (Source: Familial Cancer)
Source: Familial Cancer - February 6, 2021 Category: Cancer & Oncology Source Type: research
Current recommendations for clinical surveillance and genetic testing in rhabdoid tumor predisposition: a report from the SIOPE Host Genome Working Group
AbstractThe rhabdoid tumor (RT) predisposition syndromes 1 and 2 (RTPS1 and 2) are rare genetic conditions rendering young children vulnerable to an increased risk of RT, malignant neoplasms affecting the kidney, miscellaneous soft-part tissues, the liver and the central nervous system (Atypical Teratoid Rhabdoid Tumors, ATRT). Both, RTPS1&2 are due to pathogenic variants (PV) in genes encoding constituents of the BAF chromatin remodeling complex, i.e.SMARCB1 (RTPS1) andSMARCA4 (RTPS2). In contrast to other genetic disorders related to PVs inSMARCB1 andSMARCA4 such as Coffin-Siris Syndrome, RTPS1&2 are characterize...
Source: Familial Cancer - February 3, 2021 Category: Cancer & Oncology Source Type: research
Genetic predisposition to prostate cancer: an update
AbstractImprovements in DNA sequencing technology and discoveries made by large scale genome-wide association studies have led to enormous insight into the role of genetic variation in prostate cancer risk. High-risk prostate cancer risk predisposition genes exist in addition to common germline variants conferring low-moderate risk, which together account for over a third of familial prostate cancer risk. Identifying men with additional risk factors such as genetic variants or a positive family history is of clinical importance, as men with such risk factors have a higher incidence of prostate cancer with some evidence to ...
Source: Familial Cancer - January 24, 2021 Category: Cancer & Oncology Source Type: research
Interpretation of BRCA2 Splicing Variants: A Case Series of Challenging Variant Interpretations and the Importance of Functional RNA Analysis
We present fourBRCA2 splice site variants with complex variant interpretations (BRCA2 c.68-3T>G, c.68-2A>G, c.425G>T, c.8331+2T>C). Evidence supporting a pathogenic classification is available for each variant, including in silico models, absence in population databases, and published functional data. However, comprehensive RNA analysis showed that some functional transcript may be produced by each variant.BRCA2 c.68-3T>G results in a partial splice defect. ForBRCA2 c.68-2A>G and c.425G>T, aberrant splicing was shown to produce a potentially functional, in-frame transcript.BRCA2 c.8331+2T>C may util...
Source: Familial Cancer - January 20, 2021 Category: Cancer & Oncology Source Type: research
Progress Report: New insights into the prevention of CRC by colonoscopic surveillance in Lynch syndrome
In this report, we will discuss the implications of these new findings for the development of new surveillance protocols. (Source: Familial Cancer)
Source: Familial Cancer - January 19, 2021 Category: Cancer & Oncology Source Type: research
Comparison of universal screening in major lynch-associated tumors: a systematic review of literature
AbstractLynch syndrome (LS) is associated with an increased lifetime risk of several cancers including colorectal (CRC), endometrial (EC), ovarian (OC), urinary (UT) and sebaceous tumors (ST). The benefit for universal screening in CRC and EC is well known. However, this benefit in other major lynch-associated tumors is unclear. We performed a systematic review of all published articles in the MEDLINE database between 2005 to 2017 to identify studies performing universal screening for LS in unselected CRC, EC, OC, UT and ST. All cases with MSI-H (instability in two or more markers) or missing one or more proteins on IHC te...
Source: Familial Cancer - January 11, 2021 Category: Cancer & Oncology Source Type: research
The CAPP II trial of aspirin in Lynch syndrome/HNPCC: is it time for everyone to be treated?
(Source: Familial Cancer)
Source: Familial Cancer - January 9, 2021 Category: Cancer & Oncology Source Type: research
Genetic evaluation of patients and families with concern for hereditary endocrine tumor syndromes
AbstractHereditary endocrine tumor syndromes are rare conditions with overlapping features. It is imperative that healthcare providers differentiate between these syndromes for proper patient care. Advances in genetic testing technologies have increased utilization of genetic counseling and testing in this field; however, few endocrine cancer genetics clinics exist. Two years ago, a genetic counselor (GC) specializing in endocrine cancer genetics was added to the multidisciplinary team of the James Neuroendocrine/Thyroid Clinic at The Ohio State University. Here, we report on this experience. In total, 358 patients were se...
Source: Familial Cancer - January 7, 2021 Category: Cancer & Oncology Source Type: research
Atypical choroidal nevus in a subject with a germline PALB2 pathogenic variant
AbstractRecent evidence suggests thatPALB2 variants may increase risk for the development of uveal melanoma and uveal melanocytic neoplasms. Here we report a case of an atypical choroidal nevus in a patient with a personal history of cancer and pathogenicPALB2 germline variant. A 75-year-old white female presented with an elevated predominantly amelanotic choroidal lesion OS. On examination and ophthalmic imaging, the mass measured 8.8 mm × 6.5 mm × 1.5 mm. The mass showed predominantly medium to high reflectivity on diagnostic A-scan and acoustic hollowing on B-scan. OCT over the lesion showed no subretinal ...
Source: Familial Cancer - January 6, 2021 Category: Cancer & Oncology Source Type: research
