Neurofibromatosis type 2 discordance in monozygous twins
AbstractNeurofibromatosis type 2 (NF2) is an autosomal dominant condition caused by pathogenic variants in theNF2 gene. The pathogenic variant is either inherited or obtained by de novo mutation, characterised by the presence of schwannomas, meningiomas and ependymomas. Here we report the presence ofNF2 in one twin, with bilateral vestibular schwannomas and a pathogenic variant of theNF2 gene identified in both tumour and lymphocytes, while his monozygous brother remains asymptomatic. Imaging of the unaffected twin showed no tumour load and genetic testing via Sanger sequencing and Amplification Refractory Mutation System ...
Source: Familial Cancer - January 20, 2020 Category: Cancer & Oncology Source Type: research
De novo pathogenic germline variant in PALB2 in a patient with pancreatic cancer
AbstractDe novo mutations in the major breast/ovarian cancer susceptibility genesBRCA1 andBRCA2 are rare.De novo mutations in thePALB2 gene have never been reported. Here we report ade novo PALB2 germ line mutation (c.3455delC (p.Pro1152Hisfs*11) in a patient with pancreatic cancer, where non-paternity and somatic parental mosaicism have to the extent possible been excluded as a mechanism for detecting thede novo mutation. The lack of previous reports onde novo PALB2 mutations maybe the limited number ofPALB2germline mutations reported overall. (Source: Familial Cancer)
Source: Familial Cancer - December 18, 2019 Category: Cancer & Oncology Source Type: research
The (ir)relevance of the abandoned criterion II for the diagnosis of serrated polyposis syndrome: a retrospective cohort study
AbstractThe World Health Organization (WHO) recently updated the diagnostic criteria for serrated polyposis syndrome (SPS). One of the three previous diagnostic criteria (criterion II2010) is now abandoned: ≥ 1 serrated polyp (SP) proximal to the sigmoid in a first-degree relative (FDR) of a patient with SPS. Individuals fulfilling this abandoned criterion now receive the same surveillance recommendations as all FDRs of patients with SPS. We aimed to compare the incidence of advanced neoplasia (AN) in FDRs with vs. without fulfillment of the abandoned criterion II2010. We retrospectively recruited FDRs of patients w...
Source: Familial Cancer - December 17, 2019 Category: Cancer & Oncology Source Type: research
Renal cell carcinoma in young FH mutation carriers: case series and review of the literature
AbstractHereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is an autosomal dominant syndrome caused by heterozygous pathogenic germline variants in the fumarate hydratase (FH) gene. It is characterized by cutaneous and uterine leiomyomas and an increased risk of developing renal cell carcinoma (RCC), which is usually adult-onset. HLRCC-related RCC tends to be aggressive and can metastasize even when the primary tumor is small. Data on children and adolescents are scarce. Herein, we report two patients from unrelated Dutch families, with HLRCC-related RCC at the ages of 15 and 18 years, and a third patient with anFH ...
Source: Familial Cancer - December 1, 2019 Category: Cancer & Oncology Source Type: research
‘We don’t know for sure’: discussion of uncertainty concerning multigene panel testing during initial cancer genetic consultations
AbstractPre-test counseling about multigene panel testing involves many uncertainties. Ideally, counselees are informed about uncertainties in a way that enables them to make an informed decision about panel testing. It is presently unknown whether and how uncertainty is discussed during initial cancer genetic counseling. We therefore investigated whether and how counselors discuss and address uncertainty, and the extent of shared decision-making (SDM), and explored associations between counselors ’ communication and their characteristics in consultations on panel testing for cancer. For this purpose, consultations of co...
Source: Familial Cancer - November 25, 2019 Category: Cancer & Oncology Source Type: research
Radiotherapy-induced malignancies in breast cancer patients with TP53 pathogenic germline variants (Li –Fraumeni syndrome)
AbstractThe risk of radiotherapy-induced malignancies (RIMs) is a concern when treating Li –Fraumeni syndrome (LFS) or Li–Fraumeni Like (LFL) patients. However, the type ofTP53 pathogenic germline variant may possibly influence this risk.TP53 p.R337H mutation is particularly prevalent in Brazil. We aimed to evaluate the outcomes of patients with pathogenicTP53 variants treated for localized breast cancer in a Brazilian cohort. We evaluated retrospectively a cohort of patients with germlineTP53 pathogenic variants treated for localized breast cancer between December 1999 and October 2017. All patients were followed by t...
Source: Familial Cancer - November 19, 2019 Category: Cancer & Oncology Source Type: research
MLH1 promoter hypermethylation: are you absolutely sure about the absence of MLH1 germline mutation? About a new case
AbstractLynch syndrome accounts for 3 –5% of colorectal cancers and is due to a germline mutation in one of the mismatch repair genesMLH1,MSH2,MSH6, andPMS2. Somatic hypermethylation of theMLH1 promoter is commonly associated to sporadic cases. Strategies have been developed to identify patients with Lynch Syndrome based on clinical findings, tumoral phenotype, family history and immunohistochemistry analysis. However, there still are some pitfalls in this strategy, possibly responsible for an underdiagnosis of Lynch syndrome. Here we report the case of a 37 years-old man presenting with two concomitant tumors located in...
Source: Familial Cancer - November 18, 2019 Category: Cancer & Oncology Source Type: research
Clear cell chondrosarcoma in Von Hippel-Lindau disease
In this report, we show that clear cell chondrosarcoma may be a rare but canonical VHL manifestation through a cell-autonomous mechanism involving somatic loss-of-heterozygosity of theVHL tumor suppressor gene. We discuss the relevance of this observation with regard to the pathogenesis of clear cell chondrosarcoma in the context of VHL. (Source: Familial Cancer)
Source: Familial Cancer - October 30, 2019 Category: Cancer & Oncology Source Type: research
Long-term positive psychological outcomes in an Australian pancreatic cancer screening program
This study provides evidence of the long-term psychological benefits of PC screening in high-risk patients. There was no negative impact of screening in the short-term and the positive benefits appeared at 1-year post-intervention irrespective of scree ning result. (Source: Familial Cancer)
Source: Familial Cancer - October 16, 2019 Category: Cancer & Oncology Source Type: research
A unique case of two somatic APC mutations in an early onset cribriform-morular variant of papillary thyroid carcinoma and overview of the literature
This report presents a rare sporadic case of CMV-PTC, and to the best of our knowledge the first featuring two somaticAPC mutations underlying the disease, with an overview of CMV-PTC cases with detectedAPC andCTNNB1 pathogenic variants from the literature. (Source: Familial Cancer)
Source: Familial Cancer - October 8, 2019 Category: Cancer & Oncology Source Type: research
Novel candidates in early-onset familial colorectal cancer
This study provides potential novel candidate variants in unexplained familial CRC patients, however, functional validation is imperative to confirm the role of these variants in CRC tumorigenesis. Additionally, while whole exome sequencing enables detection of variants throughout the exome, other causes explaining the familial phenotype such as multiple single nucleotide polymorphisms accumulating to a polygenic risk or epigenetic events, might be missed with this approach. (Source: Familial Cancer)
Source: Familial Cancer - September 24, 2019 Category: Cancer & Oncology Source Type: research
Inequities in multi-gene hereditary cancer testing: lower diagnostic yield and higher VUS rate in individuals who identify as Hispanic, African or Asian and Pacific Islander as compared to European
AbstractThe identification of germline pathogenic/likely pathogenic (P/LP) variants in cancer predisposition genes can guide treatment and management decisions for the individual being tested and potentially at-risk relatives. Prior studies have raised concerns of racial/ethnic disparities in the detection rates of P/LP variants and variants of uncertain significance (VUSs). In 2018, Color Genomics ™, a commercial laboratory, made de-identified, aggregate genetic and clinical information from 50,000 individuals who completed testing for 30 cancer predisposition genes publicly available. It is the largest publicly availab...
Source: Familial Cancer - September 16, 2019 Category: Cancer & Oncology Source Type: research
Health behaviours and beliefs in individuals with familial pancreatic cancer
AbstractIndividuals at high risk for pancreatic cancer are recommended surveillance and healthy lifestyle behaviours and patient experience with recommendations are understudied. To describe engagement and experience with surveillance, tobacco and alcohol use, health beliefs and motivation (Champion Health Belief Measure) and the relationship with personal, psychosocial (Impact of Event Scale), and familial characteristics. Interest in integrative therapies (complementary therapies) are described. A multi-site cross-sectional survey including individuals at high risk for pancreatic cancer with no diagnosis of pancreatic ca...
Source: Familial Cancer - September 13, 2019 Category: Cancer & Oncology Source Type: research
Should unaffected female BRCA2 pathogenic variant carriers be told there is little or no advantage from risk reducing mastectomy?
(Source: Familial Cancer)
Source: Familial Cancer - August 22, 2019 Category: Cancer & Oncology Source Type: research
Population frequencies of pathogenic alleles of BRCA1 and BRCA2 : analysis of 173 Danish breast cancer pedigrees using the BOADICEA model
AbstractThe Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) calculates the probability that a woman carries a pathogenic variant inBRCA1 orBRCA2 based on her pedigree and the population frequencies of pathogenic alleles ofBRCA1 (0.0006394) andBRCA2 (0.00102) in the United Kingdom (UK). BOADICEA allows the clinician to define the population frequencies of pathogenic alleles ofBRCA1 andBRCA2 for other populations but only includes preset values for the Ashkenazy Jewish and Icelandic populations. Among 173 early-onset breast cancer pedigrees in Denmark, BOADICEA discriminated well ...
Source: Familial Cancer - August 20, 2019 Category: Cancer & Oncology Source Type: research
