Capillary electrophoresis as alternative method to detect tumor genetic mutations: the model built on the founder BRCA1 c.4964_4982del19 variant
In this study, we developed a rapid and reliable PCR method, coupled with capillary electrophoresis (CE) for genotyping the Italian founderBRCA1 c.4964_4982del19 (rs80359876) variant. In addition, we compared the performance of two CE platforms: (Agilent 2100 Bioanalyzer and the Experion Automated Electrophoresis system) to identify this variant. Our findings suggest that CE represents a simple and standardized diagnostic strategy for the unambiguously identification of theBRCA1 c.4964_4982del19 variant, on both germline and somatic DNA samples. The results and performance obtained by two platforms are absolutely superimpo...
Source: Familial Cancer - January 1, 2019 Category: Cancer & Oncology Source Type: research
Monoallelic MUTYH carrier status is not associated with increased breast cancer risk in a multigene panel cohort
This study aimed to determine if monoallelicMUTYH mutations are associated with increased breast cancer risk in women undergoing multigene panel testing (MGPT). The prevalence of monoallelicMUTYH mutations was compared between Non-Hispanic white female breast cancer cases (n = 30,456) and cancer-free controls (n = 12,289), all of whom underwent MGPT that includedMUTYH. We tested breast cancer associations withMUTYH alleles using Fisher ’s exact test, followed by multivariate logistic regression adjusted for age at testing and MGPT type ordered. Frequencies of the two most commonMUTYH founder mutations, p.G396D a...
Source: Familial Cancer - December 23, 2018 Category: Cancer & Oncology Source Type: research
A squamous cell carcinoma in a young woman with Lynch syndrome
AbstractLynch syndrome (LS) is an autosomal-dominant inherited disorder characterized by a predisposition to colorectal cancer and extracolonic cancers (particularly endometrium, ovary, stomach, small bowel, hepatobiliary tract, pancreas, urothelial tract, brain, and skin). Muir –Torre syndrome (MTS) is considered a phenotypical variant of LS, where patients develop sebaceous neoplasms and keratoacanthomas. Currently, only few studies and case reports suggest an association between LS and other skin cancers, such as Bowens’ disease, melanoma and squamous cell carcinoma (SCC). In this case-report we describe the case of...
Source: Familial Cancer - December 17, 2018 Category: Cancer & Oncology Source Type: research
Hereditary brain tumor with a homozygous germline mutation in PMS2 : pedigree analysis and prenatal screening in a family with constitutional mismatch repair deficiency (CMMRD) syndrome
AbstractPrecise genetic counseling and prenatal diagnosis are often hindered by incomplete penetrance of risk variance and complex patterns of inheritance. Here, we performed a clinical and genetic study of a five-generation Pakistani family with a history of multiple cases of childhood brain tumors. Six affected individuals died of brain tumors at very early ages and three were confirmed as having a homozygous mutation in exon 6 of thePMS2 gene (c.543delT). Fifteen members of the family were identified as heterozygous carriers of this mutation with a lack of cancer incidence. Both clinical manifestations and genetic test ...
Source: Familial Cancer - November 26, 2018 Category: Cancer & Oncology Source Type: research
Germline mutation p.N363K in POLE is associated with an increased risk of colorectal cancer and giant cell glioblastoma
We report a family with an autosomal dominant inheritance of PPAP due to a c.1089C>A; p.Asn363Lys mutation in the proofreading exonuclease domain ofPOLE. Ten patients presenting a history of colorectal tumours and three patients with polyposis are indexed in this family. Three carriers (including siblings and a distant cousin at 30, 45 and 52 respectively) and another member (at 37 not tested) presented glioblastoma. This is the second family reported to carry this mutation. Among the four glioblastomas in the family that we report, both show similar pathology: giant cell glioblastoma. These cases suggest that the c.108...
Source: Familial Cancer - October 27, 2018 Category: Cancer & Oncology Source Type: research
Cleft lip/palate and hereditary diffuse gastric cancer: report of a family harboring a CDH1 c.687 + 1G & gt; A germline mutation and review of the literature
This study highlights that CLP represents an important phenotypic feature ofCDH1 germline mutation carriers and emphasizes the inclusion of CLP in the HDGC testing criteria. The underlying causes for the appearance of variable phenotypes inCDH1 mutation carriers could include genetic variation, epigenetic changes and environmental factors and should be investigated in future studies. (Source: Familial Cancer)
Source: Familial Cancer - October 10, 2018 Category: Cancer & Oncology Source Type: research
Risk of multiple colorectal cancer development depends on age and subgroup in individuals with hereditary predisposition
AbstractDevelopment of multiple colorectal cancers (CRCs), synchronously or metachronously, is associated with hereditary predisposition for cancer and accurate risk estimates of multiple tumour development are relevant to recommend rational surveillance programs. A cross-sectional study design was used to estimate the risks of synchronous CRC (SCRC) and metachronous CRC (MCRC) based on data from the National Danish Hereditary Nonpolyposis Register. In total, 7100 individuals from families within the subgroups Lynch syndrome, familial CRC (FCC) and moderate risk were used with estimates relative to a non-hereditary populat...
Source: Familial Cancer - October 9, 2018 Category: Cancer & Oncology Source Type: research
Boosting care and knowledge about hereditary cancer: European Reference Network on Genetic Tumour Risk Syndromes
AbstractApproximately 27 –36 million patients in Europe have one of the ~ 5.000–8.000 known rare diseases. These patients often do not receive the care they need or they have a substantial delay from diagnosis to treatment. In March 2017, twenty-four European Reference Networks (ERNs) were launched with the aim to im prove the care for these patients through cross border healthcare, in a way that the medical knowledge and expertise travels across the borders, rather than the patients. It is expected that through the ERNs, European patients with a rare disease get access to expert care more often and more quickly , a...
Source: Familial Cancer - October 9, 2018 Category: Cancer & Oncology Source Type: research
Ovarian small cell carcinoma in one of a pair of monozygous twins
AbstractOne of a pair of monozygous twins was diagnosed and died of small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) at the age of 30 years. Her sister remained unaffected and was very concerned about her risk for developing SCCOHT. By performing comprehensive molecular analysis using whole exome sequencing (WES) approach, we showed that the deceased twin’s tumour has bi-allelic somatic genetic defects (a pathogenic frameshift deletion inSMARCA4 and LOH on chr19p). Results of WES of constitutional DNA from her unaffected sister were confirmatory. Based on our findings, we concluded that the living twin ...
Source: Familial Cancer - October 4, 2018 Category: Cancer & Oncology Source Type: research
Molecular analysis of an asbestos-exposed Belgian family with a high prevalence of mesothelioma
In this study, we report a previously undescribed Belgian family, in which BAP1 was found to be absent in the epithelial malignant mesothelial cells of the index patient. Whole exome analysis did not reveal a germline or somaticBAP1 variant. Also, no germline or somatic copy number changes in theBAP1 region could be identified. However, germline variants, predicted to be damaging, were detected in 11 other ‘Cancer census genes’ (i.e.MPL, RBM15, TET2, FAT1, HLA-A, EGFR, KMT2C, BRD3, NOTCH1, RB1 andMYO5A). Of these, the one inRBM15 seems to be the most interesting given its low minor allele frequency and absence in the g...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research
Clinical interpretation of pathogenic ATM and CHEK2 variants on multigene panel tests: navigating moderate risk
AbstractComprehensive genomic cancer risk assessment (GCRA) helps patients, family members, and providers make informed choices about cancer screening, surgical and chemotherapeutic risk reduction, and genetically targeted cancer therapies. The increasing availability of multigene panel tests for clinical applications allows testing of well-defined high-risk genes, as well as moderate-risk genes, for which the penetrance and spectrum of cancer risk are less well characterized. Moderate-risk genes are defined as genes that, when altered by a pathogenic variant, confer a 2 to fivefold relative risk of cancer. Two such genes ...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research
Gene expression analysis in peripheral blood cells of patients with hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC): identification of NRF2 pathway activation
AbstractHereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a very rare disease that is inherited in an autosomal dominant manner. Affected patients may develop from cutaneous and uterine leiomyomas to type 2 papillary renal cell carcinoma (Schmidt and Linehan, Int J Nephrol Renovasc Dis 7:253 –260, 2014). HLRCC is caused by germline mutations in theFH gene, which produces the fumarate hydratase protein that participates in the tricarboxylic acid cycle during the conversion of fumarate to malate. InFH-deficient cells, high concentrations of fumarate lead to a series of intricate events, which seem to be r...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research
Discussions about predictive genetic testing for Lynch syndrome: the role of health professionals and families in decisions to decline
AbstractUnaffected relatives of individuals with Lynch syndrome can be offered predictive genetic testing to guide surveillance recommendations. The decision-making process of those who decline testing, particularly those who do not attend a clinical genetics service, is poorly understood. We have addressed this gap by interviewing 33 individuals from Lynch syndrome mutation-carrying families, unaffected by cancer, who declined predictive genetic testing. Here, we analyse the data provided by 20 participants who unequivocally declined testing. Those who indicated they did not have enough information to make a decision or i...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research
Urological sequelae of desmoids associated with familial adenomatous polyposis
AbstractThe aim of this retrospective cohort study was to review urological complication rates arising from familial adenomatous polyposis associated desmoid tumours and their management. All patients over a 35-year period were identified from a prospectively maintained polyposis registry database and had an intra-abdominal desmoid tumour. Those without ureteric complications (n = 118, group A) were compared to those that developed ureteric obstruction (n = 40, group B) for demographics, treatment interventions and survival outcomes. 158 (56% female) patients were identified. Median age at diagnosis was 31 years ...
Source: Familial Cancer - October 1, 2018 Category: Cancer & Oncology Source Type: research
