Electronically ascertained extended pedigrees in breast cancer genetic counseling
AbstractA comprehensive pedigree, usually provided by the counselee and verified by medical records, is essential for risk assessment in cancer genetic counseling. Collecting the relevant information is time-consuming and sometimes impossible. We studied the use of electronically ascertained pedigrees (EGP). The study group comprised women (n = 1352) receiving HBOC genetic counseling between December 2006 and December 2016 at Landspitali in Iceland. EGP’s were ascertained using information from the population-based Genealogy Database and Icelandic Cancer Registry. The likelihood of being positive for the Icelandic ...
Source: Familial Cancer - March 31, 2019 Category: Cancer & Oncology Source Type: research
Pediatric craniopharyngioma in association with familial adenomatous polyposis
We report the first case of craniopharyngioma associated with FAP in a pediatric patient. A seven-year-old girl who presented with headache and vomiting was found on magnetic resonance imaging to have a suprasellar mass with cystic extension to the pre-pontine space. The tumor represented an adamantinomatous craniopharyngioma (aCP) with nuclear β-catenin expression. Whole exome sequencing confirmed aCTNNB1 activating point mutation and a germlineAPC frameshift variant. This case represents the first FAP-associated craniopharyngioma in childhood …. expanding our understanding of the molecular underpinnings driving tumori...
Source: Familial Cancer - March 26, 2019 Category: Cancer & Oncology Source Type: research
NTHL1 -associate polyposis: first Australian case report
AbstractWhile familial adenomatous polyposis accounts for approximately 1% of all colorectal cancer, the genetic cause underlying the development of multiple colonic adenomas remains unsolved in many patients. Adenomatous polyposis syndromes can be divided into: familial adenomatous polyposis,MUTYH-associated polyposis, polymerase proofreading associated polyposis and the recently describedNTHL1-associated polyposis (NAP). NAP is characterised by recessive inheritance, attenuated adenomatous polyposis, colonic cancer(s) and possible extracolonic malignancies. To date, 11 cases have been reported as having germline homozygo...
Source: Familial Cancer - March 10, 2019 Category: Cancer & Oncology Source Type: research
International society for gastrointestinal hereditary tumours —InSiGHT
(Source: Familial Cancer)
Source: Familial Cancer - March 3, 2019 Category: Cancer & Oncology Source Type: research
Progress report: familial pancreatic cancer
AbstractA hereditary predisposition to pancreatic ductal adenocarcinoma (PDAC) is reported in approximately 5% of patients. Familial pancreatic cancer (FPC) accounts for the vast majority of hereditary PDAC cases. FPC defines families with two or more affected first-degree relatives with PDAC that do not fulfil the criteria of any other inherited tumor syndrome or families with PDAC in three or more relatives of any degree. The current progress report focuses on the knowledge of FPC with regard to molecular pathogenesis, clinical and molecular diagnosis, surveillance and novel treatment options reported in the last 5 yea...
Source: Familial Cancer - February 22, 2019 Category: Cancer & Oncology Source Type: research
Implementation of a Systematic Tumor Screening Program for Lynch Syndrome in an Integrated Health Care Setting
AbstractA subset of colorectal cancer (CRC) cases are attributable to Lynch syndrome (LS), a hereditary form of CRC. Effective evaluation for LS can be done on CRC tumors to guide diagnostic testing. Increased diagnosis of LS allows for surveillance and risk reduction, which can mitigate CRC-related burden and prevent cancer-related deaths. We evaluated participation in LS screening among newly diagnosed adult CRC patients. Some cases were referred for genetics evaluation prior to study recruitment (selective screening). Those not referred directly were randomized to the intervention or control (usual care) arms. Control c...
Source: Familial Cancer - February 7, 2019 Category: Cancer & Oncology Source Type: research
Moving into the mainstream: healthcare professionals ’ views of implementing treatment focussed genetic testing in breast cancer care
This study sought to determine genetics and non-genetics specialists’ views of a proposal to mainstreamBRCA1 and2 testing in newly diagnosed breast cancer patients. Qualitative interview study. Nineteen healthcare professionals currently responsible for offering TFGT in a standard (triage + referral) pathway (breast surgeons + clinical genetics team) and oncologists preparing to offer TFGT to breast cancer patients in a mainstreamed pathway participated in in-depth interviews. Genetics and non-genetics professionals’ perceptions of mainstreaming are influenced by their vie ws of: their clinical roles and respo...
Source: Familial Cancer - January 28, 2019 Category: Cancer & Oncology Source Type: research
Mutated SON putatively causes a cancer syndrome comprising high-risk medulloblastoma combined with caf é-au-lait spots
We report the case of a boy, who was born to consanguineous parents. Prominently, he had multiple café-au-lait spots. At the age of 3 years he was diagnosed with a high-risk metastatic medulloblastoma. The patient died only 11 months after diagnosis of a fulminant relapse presenting as meningeal and spinal dissemination. Whole-exome sequencing of germline DNA was employed to detect the underlying mutation for this putative cancer syndrome presenting with the combination of medulloblastoma and skin alterations. After screening all possible homozygous gene SNVs, we identified a mutation ofSON, an essential protein in cell...
Source: Familial Cancer - January 24, 2019 Category: Cancer & Oncology Source Type: research
Phenotypic confirmation of oligodontia, colorectal polyposis and cancer in a family carrying an exon 7 nonsense variant in the AXIN2 gene
AbstractTheAXIN2 gene, likeAPC, plays a role in the Wnt signalling pathway involved in colorectal tumour formation. Heterozygous mutations inAXIN2 have been shown to cause ectodermal dysplasia (including tooth agenesis, or more specifically, oligodontia), and, in some carriers, colorectal cancer and/or adenomatous polyposis develops. There is a paucity of publishedAXIN2 families making genotype-phenotype (polyposis, colorectal cancer and oligodontia) correlations challenging. In this case report we describe a family with c.1972delA, p.Ser658Alafs*31 nonsense variant inAXIN2 where the three confirmed carriers presented with...
Source: Familial Cancer - January 22, 2019 Category: Cancer & Oncology Source Type: research
Progress report on the major clinical advances in patient-oriented research into familial melanoma (2013 –2018)
(Source: Familial Cancer)
Source: Familial Cancer - January 18, 2019 Category: Cancer & Oncology Source Type: research
Exploring the preferences of involved health professionals regarding the implementation of an online decision aid to support couples during reproductive decision-making in hereditary cancer: a mixed methods approach
AbstractTo support persons having a genetic predisposition to cancer and their partners during reproductive decision-making, an online decision aid was developed and evaluated. To maximize the impact of the support tool, this mixed methods study aims at developing the optimal implementation strategy for the decision aid. A questionnaire to assess the critical determinants that may affect this implementation was completed by health professionals involved in oncogenetic counselling (N = 46). Subsequently, semi-structured focus groups (N = 19) and individual telephonic interviews (N = 15) were performed with a su...
Source: Familial Cancer - January 17, 2019 Category: Cancer & Oncology Source Type: research
Recent advances in Lynch syndrome
AbstractLynch syndrome is one of the most common hereditary cancer predisposition syndromes and is associated with increased risks of colorectal and endometrial cancer, as well as multiple other cancer types. While the mechanism of mismatch repair deficiency and microsatellite instability and its role in Lynch-associated carcinogenesis has been known for some time, there have been significant advances recently in diagnostic testing and the understanding of the molecular pathogenesis of Lynch tumors. There is also an increased awareness that the clinical phenotype and cancer risk varies by specific mismatch repair mutation,...
Source: Familial Cancer - January 9, 2019 Category: Cancer & Oncology Source Type: research
TP53 germline mutation testing in early-onset breast cancer: findings from a nationwide cohort
AbstractEarly-onset breast cancer may be due to Li –Fraumeni Syndrome (LFS). Current national and international guidelines recommend thatTP53 genetic testing should be considered for women with breast cancer diagnosed before the age of 31 years. However, large studies investigatingTP53 mutation prevalence in this population are scarce. We collected nationwide laboratory records for all young breast cancer patients tested forTP53 mutations in the Netherlands. Between 2005 and 2016, 370 women diagnosed with breast cancer younger than 30 years of age were tested forTP53 germline mutations, and eight (2.2%) were found to...
Source: Familial Cancer - January 3, 2019 Category: Cancer & Oncology Source Type: research
Multi-gene panel testing confirms phenotypic variability in MUTYH -Associated Polyposis
We report the phenotypic spectrum of MAP in the context of multi-gene hereditary cancer panel testing. Genetic testing results and clinical histories were reviewed for individuals with biallelicMUTYH PVs detected by panel testing at a single commercial molecular diagnostic laboratory. BiallelicMUTYH PVs were identified in 82 individuals (representing 0.2% of tested individuals) with most (75/82; 91.5%) reporting a personal history of CRC and/or polyps. Ten percent (6/61) of individuals reporting polyp number reported fewer than 10 polyps and therefore did not meet current MAP testing criteria. Extracolonic cancers (21/82; ...
Source: Familial Cancer - January 2, 2019 Category: Cancer & Oncology Source Type: research
Low-level parental mosaicism in an apparent de novo case of Peutz –Jeghers syndrome
We report the case of a female found to have mosaicism for mutation in theSTK11 gene, with the mutant allele expressed in her gametes, evident by her affected offspring, and in her gastrointestinal tract demonstrated on an excised polyp analysed for diagnosis. Mosaicism for Peutz –Jeghers syndrome (PJS) has been reported in a small number of cases previously but a clinical presentation such as this has not previously been described. This finding of mosaicism was several years after initial investigations failed to identify the sameSTK11 mutation in this woman whose son was diagnosed with PJS at a young age. This case hig...
Source: Familial Cancer - January 1, 2019 Category: Cancer & Oncology Source Type: research
