Clinical phenotypes combined with saturation genome editing identifying the pathogenicity of BRCA1 variants of uncertain significance in breast cancer
AbstractCharacterizing the pathogenicity ofBRCA1 variants of uncertain significance (VUSs) is a major bottleneck in clinical management ofBRCA1-associated breast cancer. Saturation genome editing (SGE) was recently reported as an innovative laboratory-based approach to assess the pathogenicity ofBRCA1 variants. We combined clinical phenotypes and SGE score to identify the pathogenicity ofBRCA1 VUSs detected in a cohort of 8,085 breast cancer patients. According to SGE function score, 33 out of 144BRCA1 VUSs detected were classified into “loss of function” (n = 13), “intermediate” (n = 2), and “functional...
Source: Familial Cancer - August 16, 2020 Category: Cancer & Oncology Source Type: research
Is a colorectal neoplasm diagnosis a trigger to change dietary and other lifestyle habits for persons with Lynch syndrome? A prospective cohort study
AbstractA cancer diagnosis is suggested to be associated with changes in dietary and lifestyle habits. Whether this applies to persons with familial cancer, such as Lynch syndrome (LS) is unknown. We investigated whether a colorectal neoplasm (CRN) diagnosis in persons with LS is associated with changes in dietary and lifestyle habits over time. We used data of confirmed LS mutation carriers from the GEOLynch study, a prospective cohort study. Information on dietary intake and lifestyle habits was collected with a validated semi-quantitative food frequency questionnaire and a general questionnaire administered at baseline ...
Source: Familial Cancer - August 7, 2020 Category: Cancer & Oncology Source Type: research
Recent advances in Lynch syndrome
(Source: Familial Cancer)
Source: Familial Cancer - August 7, 2020 Category: Cancer & Oncology Source Type: research
Barriers and facilitators to CDH1 carriers contemplating or undergoing prophylactic total gastrectomy
This study examined factors related to decision-making about PTG in three groups of individuals who: (1) underwent PTG immediately after receiving genetic testing results; (2) delayed PTG by ≥ 1 year or; (3) declined PTG. Participants were recruited from a familial gastric cancer registry at a tertiary care hospital. Patients withCDH1 pathogenic or likely pathogenic variants who contemplated and/or underwent PTG were eligible. 24 individuals contemplated PTG: 9 had immediate surgery (within a year), 8 delayed surgery, and 7 declined surgery. Data on PTG barriers and facilitators were obtained on all participants using...
Source: Familial Cancer - August 4, 2020 Category: Cancer & Oncology Source Type: research
Characterizing germline APC and MUTYH variants in Ashkenazi Jews compared to other individuals
AbstractGermline variants in theAPC andMUTYH genes contribute to colorectal cancer (CRC) and adenoma risk, though may occur with varying frequencies in individuals of different ancestries. The aim of this study was to evaluate the prevalence ofAPC, monoallelicMUTYH and biallelicMUTYH germline variants in Ashkenazi Jewish (AJ) and Other Ancestry (OA) individuals with colorectal adenomas. We studied 7225 individuals with colorectal adenomas who had germlineAPC andMUTYH testing at a commercial laboratory. Cross-sectional medical history data were extracted from provider-completed test requisition forms. We performed bivariate...
Source: Familial Cancer - August 2, 2020 Category: Cancer & Oncology Source Type: research
Recent advances in Lynch syndrome: response to M øller et al.
(Source: Familial Cancer)
Source: Familial Cancer - August 2, 2020 Category: Cancer & Oncology Source Type: research
Multiple primary cancers (renal papillary, lymphoma and teratoma) and hepatic cysts in association with a pathogenic germline mutation in the MET gene
AbstractActivating germline mutations of theMET gene are associated with hereditary papillary renal cancer. This a very rare autosomal dominant condition, which is usually considered not to display a phenotype of multiple types of malignancy. However, this report describes the case of a man who has been affected with testicular teratoma, diffuse large B-cell lymphoma and multiple hepatic cysts, as well as multiple papillary renal cancers. There is good supporting evidence for roles of over-expression/activity of the HGF/MET ligand-receptor in development of these tumours, raising the possibility of other increased cancer r...
Source: Familial Cancer - July 19, 2020 Category: Cancer & Oncology Source Type: research
Complete response of hereditary leiomyomatosis and renal cell cancer (HLRCC)-associated renal cell carcinoma to nivolumab and ipilimumab combination immunotherapy by: a case report
We report an aggressive RCC case in a 49-year-old man. Nine weeks after undergoing a total nephroureterectomy of the right kidney, he had a metastasectomy at port site. Within 14 weeks of the initial surgery, multiple recurrent tumors developed in the right retroperitoneal space. The pathological diagnosis was FH-deficient RCC. Genetic testing identified a heterozygous germline mutation ofFH (c.641_642delTA), which confirmed the diagnosis of HLRCC-RCC. He received combination therapy with the immune checkpoint inhibitors (ICIs) nivolumab and ipilimumab as the first-line therapy. After 31 weeks of ICI treatment, a complete ...
Source: Familial Cancer - July 14, 2020 Category: Cancer & Oncology Source Type: research
Report of the fifth meeting of the European Consortium 'Care for CMMRD' (C4CMMRD), Leiden, The Netherlands, July 6th 2019
(Source: Familial Cancer)
Source: Familial Cancer - July 1, 2020 Category: Cancer & Oncology Source Type: research
Improving primary care identification of familial breast cancer risk using proactive invitation and decision support
This study demonstrated proactive risk assessment in primary care enables accurate identification of women, including many younger women, at increased risk of breast cancer. To improve generalisability across the population, more active me thods of engagement need to be explored.Trial registration: CRUK Clinical Trials Database 11779. (Source: Familial Cancer)
Source: Familial Cancer - June 10, 2020 Category: Cancer & Oncology Source Type: research
Chemoprevention in familial adenomatous polyposis: past, present and future
AbstractFamilial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome characterized by colorectal adenomas and a near 100% lifetime risk of colorectal cancer (CRC). Prophylactic colectomy, usually by age 40, is the gold-standard therapy to mitigate this risk. However, colectomy is associated with morbidity and fails to prevent extra-colonic disease manifestations, including gastric polyposis, duodenal polyposis and cancer, thyroid cancer, and desmoid disease. Substantial research has investigated chemoprevention medications in an aim to prevent disease progression, postponing the need for colectomy and ...
Source: Familial Cancer - June 7, 2020 Category: Cancer & Oncology Source Type: research
Prospective observational data informs understanding and future management of Lynch syndrome: insights from the Prospective Lynch Syndrome Database (PLSD)
AbstractThe Prospective Lynch Syndrome Database (PLSD) has been developed as an international, multicentre, prospective, observational study that aims to provide age and organ-specific cancer risks according to gene and gender, estimates of survival after cancer and information on the effects of interventions. Recent reports from PLSD provided improved estimates of cancer risks and survival and showed that different time intervals between surveillance colonoscopies did not affect the incidence, stage or prognosis of colorectal cancer. The PLSD reports suggest that current management guidelines for Lynch syndrome should be ...
Source: Familial Cancer - June 7, 2020 Category: Cancer & Oncology Source Type: research
Germline variants discovered in lymphoma patients undergoing tumor profiling: a case series
AbstractClinical tumor sequencing protocols often depend on obtaining germline DNA from patients to aid in the identification of de novo variants in the tumor, and therefore come with the possibility for the incidental discovery of germline variants. Ninety-one adult patients with lymphoma were consented and enrolled in MIONCOSEQ, an IRB-approved tumor profiling protocol that utilizes an exome sequencing platform. Charts were retrospectively reviewed for germline variants from sequencing results, personal and/or family history of cancer and genetic counseling referral. After review of the 91 lymphoma cases, seven (8%) case...
Source: Familial Cancer - June 5, 2020 Category: Cancer & Oncology Source Type: research
Two cases of somatic STK11 mosaicism in Danish patients with Peutz –Jeghers syndrome
We report two Danish patients withSTK11 mosaicism detected in blood when using Next-Generation Sequencing. This is only the sixth and seventh patient reported in the literature, and we compare phenotypes of the reported cases. The results indicate thatSTK11 mosaicism is more frequent than anticipated and highlight that mosaicism should be considered in patients with clinical suspicion of PJS or patients fulfilling the diagnostic criteria. (Source: Familial Cancer)
Source: Familial Cancer - June 5, 2020 Category: Cancer & Oncology Source Type: research
Constitutional mosaicism for a BRCA2 mutation as a cause of early-onset breast cancer
We report on a breast cancer patient with constitutional somatic mosaicism of aBRCA2 mutation.BRCA2 mutation c.9294C>G, p.(Tyr3098Ter) was detected in 20% of reads in DNA extracted from peripheral blood using next-generation sequencing (NGS). TheBRCA2 mutation was subsequently observed at similar levels in normal breast tissue, adipose tissue, normal right fallopian tube tissue and ovaries of the patient, suggesting that this mutation occurred early in embryonic development. This is the first case to report constitutional mosaicism for aBRCA2 mutation and shows thatBRCA2 mosaicism can underlie early-onset breast cancer....
Source: Familial Cancer - May 27, 2020 Category: Cancer & Oncology Source Type: research
