Screening of RET gene mutations in Chinese patients with medullary thyroid carcinoma and their relatives
This study investigated the spectrum of germline RET mutations and clinical features in Chinese hereditary MTC patients. A total of 53 family members from 11 different hereditary MTC families were recruited for detection of RET exon 8, 10, 11, 13, 14, 15, and 16 mutations, in genomic DNA from peripheral blood leucocytes using polymerase chain reaction (PCR) and direct DNA sequencing. Of the 53 participants, eight different germline RET mutations were detected in 37 individuals. These RET mutations were distributed in exons 10, 11, 13, and 16. The most frequent RET mutation was localized at exon 11 codon 634 (67.6 %; 2...
Source: Familial Cancer - August 9, 2015 Category: Cancer & Oncology Source Type: research

POLE mutations in families predisposed to cutaneous melanoma
Abstract Germline mutations in the exonuclease domain of POLE have been shown to predispose to colorectal cancers and adenomas. POLE is an enzyme involved in DNA repair and chromosomal DNA replication. In order to assess whether such mutations might also predispose to cutaneous melanoma, we interrogated whole-genome and exome data from probands of 34 melanoma families lacking pathogenic mutations in known high penetrance melanoma susceptibility genes: CDKN2A, CDK4, BAP1, TERT, POT1, ACD and TERF2IP. We found a novel germline mutation, POLE p.(Trp347Cys), in a 7-case cutaneous melanoma family. Functional assays in ...
Source: Familial Cancer - August 6, 2015 Category: Cancer & Oncology Source Type: research

Risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a 30-year semi-prospective analysis
Abstract BRCA1 and BRCA2 mutation carriers have an increased risk of contralateral breast cancer after primary breast cancer. Risk reduction strategies are discussed after assessment of risk factors for developing contralateral breast cancer. We assessed potential risk factors that could be of use in clinical practice, including the novel use of single nucleotide polymorphisms (SNP) testing. 506 BRCA1 and 505 BRCA2 mutation carriers with a diagnosis of breast cancer were observed for up to 30 years. The risk of a contralateral breast cancer is approximately 2–3 % per year, remaining ...
Source: Familial Cancer - August 4, 2015 Category: Cancer & Oncology Source Type: research

Risk of colorectal cancer for people with a mutation in both a MUTYH and a DNA mismatch repair gene
Abstract The base excision repair protein, MUTYH, functionally interacts with the DNA mismatch repair (MMR) system. As genetic testing moves from testing one gene at a time, to gene panel and whole exome next generation sequencing approaches, understandin g the risk associated with co-existence of germline mutations in these genes will be important for clinical interpretation and management. From the Colon Cancer Family Registry, we identified 10 carriers who had both a MUTYH mutation (6 with c.1187G>A p.(Gly396Asp), 3 with c.821G>A p.(Arg274Gln), and 1 with c.536A>G p.(Tyr179Cys)) and a MMR gene mut...
Source: Familial Cancer - July 23, 2015 Category: Cancer & Oncology Source Type: research

Risk reducing salpingectomy and delayed oophorectomy in high risk women: views of cancer geneticists, genetic counsellors and gynaecological oncologists in the UK
We report on the acceptability/attitude of UK health professionals towards RRSDO. An anonymised web-based survey was sent to UK Cancer Genetics Group (CGG) and British Gynaecological Cancer Society (BGCS) members to assess attitudes towards RRSDO. Baseline characteristics were described using descriptive statistics. A Chi square test was used to compare categorical, Kendal-tau-b test for ordinal and Mann–Whitney test for continuous variables between two groups. 173/708 (24.4 %) of invitees responded. 71 % respondents (CGG = 57 %/BGCS = 83 %, p = 0.005) agreed with the...
Source: Familial Cancer - July 16, 2015 Category: Cancer & Oncology Source Type: research

Metastatic sympathetic paraganglioma in a patient with loss of the SDHC gene
Abstract Mutation of the genes encoding the succinate dehydrogenase (SDH) subunits A, B, C, or D, or the SDHAF2 protein, cause the SDHx-hereditary paraganglioma syndromes. Hereditary susceptibility to metastatic sympathetic pheochromocytomas and paragangliomas is most commonly due to germline mutations in the SDHB gene. Individuals with SDHD mutations occasionally present with metastatic disease, while conversely malignant paragangliomas are rarely observed in SDHC carriers. A 43 year-old woman presented with an abdominal paraganglioma metastatic to the skeleton and multiple lymph nodes. The tumor produced ex...
Source: Familial Cancer - July 11, 2015 Category: Cancer & Oncology Source Type: research

Massive gastric polyposis associated with a germline SMAD4 gene mutation
Abstract Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by the development of multiple hamartomatous polyps in the gastrointestinal tract. Polyps are most common in the colorectum (98 % of patients) and the stomach (14 %). Causative mutations for JPS have been identified in two genes to date, SMAD4 and BMPR1A. SMAD4 mutations are associated with a higher incidence of gastric polyposis. In this case report, we describe two patients with massive gastric polyposis associated with a SMAD4 mutation. Both presented with anaemia and both had colonic polyps. Initial endosco...
Source: Familial Cancer - July 10, 2015 Category: Cancer & Oncology Source Type: research

Challenges to clinical utilization of hereditary cancer gene panel testing: perspectives from the front lines
Abstract Next generation sequencing (NGS) technology is rapidly being implemented into clinical practice. Qualitative research was performed to gain an improved understanding of the landscape surrounding the use of NGS in cancer genetics. A focus group was conducted at the Wisconsin Cancer Risk Programs Network biannual meeting. Free flowing discussion with occasional open-ended questions provided insights into the use of NGS. 19 genetic counselors and medical professionals participated. Three major themes were identified with respect to NGS and its use in cancer genetics: knowledge gaps, the evolving clinician ro...
Source: Familial Cancer - June 25, 2015 Category: Cancer & Oncology Source Type: research

High accuracy of family history of melanoma in Danish melanoma cases
We examined the family history of 181 melanoma probands who reported 199 cases of melanoma in relatives, of which 135 cases where in first degree relatives. We confirmed the diagnosis of melanoma in 77 % of all relatives, and in 83 % of first degree relatives. In 181 probands we validated the negative family history of melanoma in 748 first degree relatives and found only 1 case of melanoma which was not reported in a 3 case melanoma family. Melanoma patients in Denmark report family history of melanoma in first and second degree relatives with a high level of accuracy with a true positive predictive value betwee...
Source: Familial Cancer - June 21, 2015 Category: Cancer & Oncology Source Type: research

BRCA1 gene variant p.P142H associated with male breast cancer: a two-generation genealogic study and literature review
Abstract Breast cancer occurs rarely in male patient. BRCA1 gene mutation seems to be related to male breast cancer, but its role is not clearly defined. We have identified in a male patient affected by breast cancer the BRCA1 gene variant p.P142H. We performed a literature research using the keywords “male breast cancer”, “male breast cancer mutations” and “BRCA” and we reviewed the cases. We found ew other studies regarding BRCA1 variant p.P142H, about female subjects. At the moment, BRCA1 gene variant p.P142H is not certainly classified as neutral or deleterious. Genetic test...
Source: Familial Cancer - June 18, 2015 Category: Cancer & Oncology Source Type: research

Supporting families with Cancer: A patient centred survivorship model of care
Abstract In 2011, the Leicestershire Clinical Genetics Department in collaboration with Macmillan Cancer Support initiated a project called Supporting Families with Cancer (SFWC). The project aimed to raise awareness of inherited cancers amongst both healthcare professionals and the general public and develop a patient-centred collaborative approach to cancer treatment and support services. This paper describes the project’s development of a range of community outreach events and a training scheme for primary healthcare professionals designed to improve familial cancer referral rates in Leicester. Follow...
Source: Familial Cancer - June 16, 2015 Category: Cancer & Oncology Source Type: research

Coexistence of paraganglioma/pheochromocytoma and papillary thyroid carcinoma: a four-case series analysis
Abstract The paraganglioma (PGL)/pheochromocytoma (PHEO)—papillary thyroid carcinoma (PTC) dyad has been reported rarely. Whether the association is coincidental or results from an underlying genetic predisposition is difficult to ascertain. We analyzed clinical and molecular data on four unrelated patients identified and treated by one of us (MJB) at a tertiary center. Patients were screened for germline variants in a panel of candidate genes: RET, VHL, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, PTEN, CDKN1B. All patients were female; median age at diagnosis of PGL/PHEO was 45 years and at diagnosis of PT...
Source: Familial Cancer - June 14, 2015 Category: Cancer & Oncology Source Type: research

Follicular variant of papillary thyroid cancer in Alström syndrome
We report a 35-year-old woman with known history of AS, who developed a follicular variant of papillary thyroid carcinoma. To our knowledge this is the first association of AS with thyroid malignancy, among the approximately 450 cases reported since the first description of the syndrome. We conclude that papillary thyroid carcinoma should be considered in the differential diagnosis of thyroid nodules in patients with AS. (Source: Familial Cancer)
Source: Familial Cancer - June 5, 2015 Category: Cancer & Oncology Source Type: research

BRCA1 and BRCA2 mutations in males with familial breast and ovarian cancer syndrome. Results of a Spanish multicenter study
Abstract Male breast cancer (MBC) is a rare disease that represents
Source: Familial Cancer - May 31, 2015 Category: Cancer & Oncology Source Type: research

International society for gastrointestinal hereditary tumours—InSiGHT
(Source: Familial Cancer)
Source: Familial Cancer - May 19, 2015 Category: Cancer & Oncology Source Type: research

A functional HOTAIR rs920778 polymorphism does not contributes to gastric cancer in a Turkish population: a case–control study
Abstract An aberrant up-regulation of HOX transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA (lncRNA), is associated with human cancers including gastric cancer (GC) and worse clinicopathological features. A naturally occurring functional single nucleotide polymorphism (SNP) rs920,778 (C→T) in the intronic enhancer of HOTAIR gene has been demonstrated to affect HOTAIR expression and cancer susceptibility. To investigate the association of the HOTAIR rs920778 polymorphism on the risk of GC susceptibility in Turkish population, a hospital-based case–control study was carried out consistin...
Source: Familial Cancer - May 17, 2015 Category: Cancer & Oncology Source Type: research

Psychological distress related to BRCA testing in ovarian cancer patients
In conclusion, the specific types of worry and distress most relevant to receiving genetic testing irrespective of family history were not captured by the generic distress instruments. The MICRA was supported as a useful tool for detection of mental distress related to genetic testing and risk evaluation. (Source: Familial Cancer)
Source: Familial Cancer - May 16, 2015 Category: Cancer & Oncology Source Type: research

Prevalence and detection of psychosocial problems in cancer genetic counseling
Abstract Only a minority of individuals who undergo cancer genetic counseling experience heightened levels of psychological distress, but many more experience a range of cancer genetic-specific psychosocial problems. The aim of this study was to estimate the prevalence of such psychosocial problems, and to identify possible demographic and clinical variables associated significantly with them. Consenting individuals scheduled to undergo cancer genetic counseling completed the Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire, the Hospital Anxiety and Depression Scale (HADS) and the Distress Thermomete...
Source: Familial Cancer - May 13, 2015 Category: Cancer & Oncology Source Type: research

Childhood cancers in families with and without Lynch syndrome
Abstract Inheritance of a germline mutation in one of the DNA mismatch repair (MMR) genes or the EPCAM gene is associated with an increased risk of colorectal cancer, endometrial cancer, and other adult malignancies (Lynch syndrome). The risk of childhood cancers in Lynch syndrome families, however, is not well studied. Using data from the Colon Cancer Family Registry, we compared the proportion of childhood cancers (diagnosed before 18 years of age) in the first-, second-, and third-degree relatives of 781 probands with a pathogenic mutation in one of the MMR genes; MLH1 (n = 275), MSH2 (n&nb...
Source: Familial Cancer - May 11, 2015 Category: Cancer & Oncology Source Type: research

Survival in familial colorectal cancer: a Danish cohort study
Abstract The monogenic Lynch syndrome (LS) is associated with better survival in colorectal cancer (CRC) patients. Whether family history of CRC affects CRC prognosis in general remains unclear. We evaluated overall mortality in a Danish cohort of CRC patients comparing patients with a family history (FHpos) to those without (FHneg) with focus on patients from non-syndromic families, thus FHpos patients were further divided into a non-syndromic group (FHNS) and a HNPCC/LS group (FHHNPCC). We included CRC patients diagnosed 1995–1998. First degree relatives were identified using Danish population registries a...
Source: Familial Cancer - May 11, 2015 Category: Cancer & Oncology Source Type: research

Genotype–phenotype analysis of von Hippel–Lindau syndrome in fifteen Indian families
Abstract The general prevalence of the familial multi-organ tumor disorder, von Hippel–Lindau syndrome (VHL), was estimated to be 1 in 25–40,000 in western studies two decades back. Few studies were done in Indian sub-continent, amidst a surge in clinical reports on VHL specific manifestations. The syndrome is correlated with mutations of the gene VHL (located in Chr 3p25.3). We aimed to conduct a prospective case series describing phenotypic and genotypic characteristics in Indian population. The VHL-specific clinical and radiological features were collected from patients and family members. Genotypic...
Source: Familial Cancer - May 8, 2015 Category: Cancer & Oncology Source Type: research

Birt–Hogg–Dubé syndrome and intracranial vascular pathologies
We present the only known cases of intracranial vascular pathologies in patients with Birt–Hogg–Dubé syndrome. We present three cases (three female; age range 18–50) of intracranial vascular lesions in Birt–Hogg–Dubé patients, including two aneurysms and one arteriovenous malformation, and review one previously reported case of carotid aplasia. Due to the rarity of Birt–Hogg–Dubé syndrome and significant variations in its clinical presentation, it is difficult to assess whether or not Birt–Hogg–Dubé patients are predisposed to intracranial va...
Source: Familial Cancer - May 8, 2015 Category: Cancer & Oncology Source Type: research

3′-UTR poly(T/U) repeat of EWSR1 is altered in microsatellite unstable colorectal cancer with nearly perfect sensitivity
Abstract Approximately 15 % of colorectal cancers exhibit instability of short nucleotide repeat regions, microsatellites. These tumors display a unique clinicopathologic profile and the microsatellite instability status is increasingly used to guide clinical management as it is known to predict better prognosis as well as resistance to certain chemotherapeutics. A panel of five repeats determined by the National Cancer Institute, the Bethesda panel, is currently the standard for determining the microsatellite instability status in colorectal cancer. Recently, a quasimonomorphic mononucleotide repeat 16T/U at...
Source: Familial Cancer - May 1, 2015 Category: Cancer & Oncology Source Type: research

A novel POLE mutation associated with cancers of colon, pancreas, ovaries and small intestine
Abstract In some families there is an increased risk for colorectal cancer, caused by heritable, but often unidentified genetic mutations predisposing to the disease. We have identified the likely genetic cause for disease predisposition in a large family with high burden of colorectal adenomas and carcinomas, in addition to extra-colonic cancers. This family had previously been tested for known cancer susceptibility genes, with negative results. Exome sequencing was used to identify a novel mutation, c.1373A>T (p.Tyr458Phe), in the gene for DNA polymerase epsilon catalytic subunit (POLE). This mutation is loca...
Source: Familial Cancer - April 10, 2015 Category: Cancer & Oncology Source Type: research

Zebrafish xenotransplantation as a tool for in vivo cancer study
Abstract Zebrafish represents a powerful model for cancer research. Particularly, the xenotransplantation of human cancer cells into zebrafish has enormous potential for further evaluation of cancer progression and drug discovery. Various cancer models have been established in adults, juveniles and embryos of zebrafish. This xenotransplantation zebrafish model provides a unique opportunity to monitor cancer proliferation, tumor angiogenesis, metastasis, self-renewal of cancer stem cells, and drug response in real time in vivo. This review summarizes the use of zebrafish as a model for cancer xenotransplantation, a...
Source: Familial Cancer - April 10, 2015 Category: Cancer & Oncology Source Type: research

Specific Alu elements involved in a significant percentage of copy number variations of the STK11 gene in patients with Peutz–Jeghers syndrome
Abstract Peutz–Jeghers syndrome (PJS) is a rare hereditary syndrome characterized by the occurrence of hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation and increased risk of cancer in multiple internal organs. PJS is preconditioned by the manifestation of mutations in the STK11 gene. The majority of detected STK11 changes are small scale mutations, however recent studies showed the significant contribution of medium-sized changes commonly known as copy number variations (CNVs). Here we present a novel 7001 bps deletion of STK11 gene fragment, in which we identified the prese...
Source: Familial Cancer - April 4, 2015 Category: Cancer & Oncology Source Type: research

Risk factors for endometrial cancer among women with a BRCA1 or BRCA2 mutation: a case control study
The objective of this study was to assess the impact of these medications and other risk factors on endometrial cancer risk in BRCA carriers. Women with a BRCA1 or BRCA2 mutation were identified from a registry of mutation carriers. Cases were 83 women who had a diagnosis of endometrial cancer. Controls were 1027 matched women who did not develop endometrial cancer and who had an intact uterus. All women completed a baseline questionnaire, which included questions about ages at menarche and menopause, oral contraceptive use, hormone replacement therapy use, hysterectomy, oophorectomy, breast cancer history and tamoxifen us...
Source: Familial Cancer - April 3, 2015 Category: Cancer & Oncology Source Type: research

Increased risk for colorectal adenomas and cancer in mono-allelic MUTYH mutation carriers: results from a cohort of North-African Jews
In conclusion, MUTYH mutations are prevalent among Jews of North-African origin with colorectal adenomas with or without early onset CRC. Mono-allelic MUTYH carriers with a family history of cancer had a clinical phenotype that varied from having only few adenomas to multiple (>10) adenomas. These findings support MUTYH testing in patients with even few adenomas and suggest the consideration of increased surveillance in mono-allelic carriers with a family history of cancer. (Source: Familial Cancer)
Source: Familial Cancer - March 30, 2015 Category: Cancer & Oncology Source Type: research

Implementing a telephone based peer support intervention for women with a BRCA1/2 mutation
We describe the implementation of a peer-support program that aims to reduce distress among women with a BRCA1/2 mutation, including peer and support recipient satisfaction with the program, challenges and lessons learnt. Participants with a BRCA1/2 mutation were matched with a trained peer volunteer (also a mutation carrier) to have regular one-on-one phone calls, over 4 months. Details of the calls, including topics discussed, time spent and number, were collected. Peers and recipients completed surveys assessing how they felt the contact went, satisfaction with the program, and preferences for matching. Satisfactio...
Source: Familial Cancer - March 29, 2015 Category: Cancer & Oncology Source Type: research

Erratum to: Mutations of HNRNPA0 and WIF1 predispose members of a large family to multiple cancers
(Source: Familial Cancer)
Source: Familial Cancer - March 28, 2015 Category: Cancer & Oncology Source Type: research

Germline mutations predisposing to non-small cell lung cancer
Abstract Lung cancer in multiple first degree relatives had previously been attributed to smoking and to inherited enzymes associated with increased activation of carcinogens in smoke. There was not clear agreement on the significance of the testing methods for lung cancer susceptibility. More recent studies have identified germline mutations associated with lung cancer even in the absence of smoking and other mutations with plausible explanations for their association with lung cancer caused by smoking. At this time, the clinical significance of the various germline mutations for screening and the implications fo...
Source: Familial Cancer - March 27, 2015 Category: Cancer & Oncology Source Type: research

Validation of an online questionnaire for identifying people at risk of familial and hereditary colorectal cancer
Abstract We developed and validated an online questionnaire to document familial cancer history, in order to facilitate the detection of persons with a familial or hereditary colorectal cancer (CRC) risk. The development of the self-administered online questionnaire for the assessment of familial and hereditary CRC risk was based on nationwide criteria for referral to genetic specialists due to a Lynch syndrome suspicion, as well as existing criteria for surveillance colonoscopies because of an increased risk of familial CRC. The questionnaire was validated at a private colonoscopy center. Patients scheduled for c...
Source: Familial Cancer - March 24, 2015 Category: Cancer & Oncology Source Type: research

Clinical characterization and mutation spectrum in Caribbean Hispanic families with Lynch syndrome
This report presents the first description of the mutation spectrum and clinicopathologic characteristics of LS Caribbean Hispanics patients. (Source: Familial Cancer)
Source: Familial Cancer - March 18, 2015 Category: Cancer & Oncology Source Type: research

Pitfalls in the diagnosis of biallelic PMS2 mutations
Abstract Constitutional Mismatch Repair Deficiency (CMMR-D) syndrome is an inherited childhood cancer syndrome due to bi-allelic mutations in one of the four DNA mismatch repair genes involved in Lynch syndrome. The tumor spectrum of this syndrome includes hematological, brain and Lynch syndrome associated malignancies, with an increased risk of synchronous and metachronous cancers, and signs of Neurofibromatosis type-1 syndrome such as café-au-lait macules during the first three decades of life. Here, we report the first Argentinian patient with CMMR-D syndrome, focusing on her history of cancer and gastro...
Source: Familial Cancer - March 15, 2015 Category: Cancer & Oncology Source Type: research

Genetic screening in patients with Retinoblastoma in Israel
Abstract Retinoblastoma (Rb) is a childhood tumor (~1 in 20,000 live births) developing in the retina due to mutations in the RB1 gene. Identification of the oncogenic mutations in the RB1 gene is important for the clinical management and for genetic counseling to families with a child or a parent affected with the tumor. Here we present our experience in detecting the pathogenic mutations in blood samples, from 150 unrelated Rb patients and highlight the relevant counseling issues. Mutation screening in the RB1 gene was based on Sanger sequencing, mosaicism of recurrent CpG transition mutations was detected by al...
Source: Familial Cancer - March 10, 2015 Category: Cancer & Oncology Source Type: research

Mismatch repair deficient-crypts in non-neoplastic colonic mucosa in Lynch syndrome: insights from an illustrative case
Abstract Mono-allelic germline mutations in DNA mismatch repair (MMR) genes lead to Lynch syndrome (LS). Questions remain as to the timing of the inactivation of the wild-type allele in LS-associated tumorigenesis. Speculation exists that it happens after the neoplasia has been initiated. However, a recent study reported the presence of MMR-deficiency in non-neoplastic colonic crypts in LS; thus the possibility can be raised that these crypts may be tumor precursors, and as such, biallelic loss of MMR may occur prior to neoplasia. Here we report a unique case that showed findings supporting both of the two seemin...
Source: Familial Cancer - March 1, 2015 Category: Cancer & Oncology Source Type: research

Gly322Asp and Asn127Ser single nucleotide polymorphisms (SNPs) of hMSH2 mismatch repair gene and the risk of triple-negative breast cancer in Polish women
In this report we genotyped two polymorphisms of hMSH2 DNA repair gene in 70 TNBC patients and 70 age-matched cancer-free women using RFLP–PCR. The following polymorphisms were studied: an A/G transition at 127 positions producing an Asn/Ser substitution at codon 127 (the Asn127Ser polymorphism, rs17217772) and a G/A transition at 1032 position resulting in a Gly/Asp change at codon 322 (the Gly322Asp polymorphism, rs4987188). We found an association between the hMSH2 Asp/Asp and Gly/Asp genotypes and TNBC occurence. Variant Asp allele of hMSH2 decreased cancer risk [odds ratio (OR) 0.11; 95 % confidence interva...
Source: Familial Cancer - March 1, 2015 Category: Cancer & Oncology Source Type: research

APC rearrangements in familial adenomatous polyposis: heterogeneity of deletion lengths and breakpoint sequences underlies similar phenotypes
Abstract Familial adenomatous polyposis (FAP) is a dominantly inherited syndrome leading to the development of multiple intestinal polyps and colorectal cancer. FAP is associated with germline defects of APC tumor suppressor gene; although truncating mutations account for the majority of cases, large APC deletions represent a common disease-causing defect. While a number of intragenic deletions have been well-characterized, sequencing data of breakpoints involved in large APC rearrangements are extremely scanty. We characterized six deletions identified by multiplex ligation-dependent probe amplification (three i...
Source: Familial Cancer - March 1, 2015 Category: Cancer & Oncology Source Type: research

Detection of inherited mutations for hereditary cancer using target enrichment and next generation sequencing
Abstract Hereditary cancers occur because of inherited gene mutations. Genetic testing has been approved to provide information for risk assessment and rationale for appropriate intervention. Testing methods currently available for clinical use have some limitations, including sensitivity and testing throughput, etc. Next generation sequencing (NGS) has been rapidly evolving to increase testing sensitivity and throughput. It can be potentially used to identify inherited mutation in clinical diagnostic setting. Here we develop an effective method employing target enrichment and NGS platform to detect common as wel...
Source: Familial Cancer - March 1, 2015 Category: Cancer & Oncology Source Type: research

Identification of a breast cancer family double heterozygote for RAD51C and BRCA2 gene mutations
This study illustrates the advantage of sequencing gene panels using next-generation sequencing in terms of genetic testing. (Source: Familial Cancer)
Source: Familial Cancer - March 1, 2015 Category: Cancer & Oncology Source Type: research

The analysis of a large Danish family supports the presence of a susceptibility locus for adenoma and colorectal cancer on chromosome 11q24
Abstract Hereditary colorectal cancer accounts for approximately 30 % of all colorectal cancers, but currently only 5 % of these families can be explained by highly penetrant, inherited mutations. In the remaining 25 % it is not possible to perform a gene test to identify the family members who would benefit from prophylactic screening. Consequently, all family members are asked to follow a screening program. The purpose of this study was to localize a new gene which causes colorectal cancer. We performed a linkage analysis using data from a SNP6.0 chip in one large family with 12 affected family me...
Source: Familial Cancer - February 28, 2015 Category: Cancer & Oncology Source Type: research

Mutations of HNRNPA0 and WIF1 predispose members of a large family to multiple cancers
Abstract We studied a large family that presented a strong familial susceptibility to multiple early onset cancers including prostate, breast, colon, and several other uncommon cancers. Through targeted gene, linkage, and whole genome sequencing analyses, we show that the presence of a variant in the regulatory region of HNRNPA0 associated with elevated cancer incidence in this family (Hazard ratio = 7.20, p = 0.0004). Whole genome sequencing identified a second rare protein changing mutation of WIF1 that interacted with the HNRNPA0 variant resulting in extremely high risk for cancer in carrier...
Source: Familial Cancer - February 26, 2015 Category: Cancer & Oncology Source Type: research

The importance of proper bioinformatics analysis and clinical interpretation of tumor genomic profiling: a case study of undifferentiated sarcoma and a constitutional pathogenic BRCA2 mutation and an MLH1 variant of uncertain significance
Abstract Next-generation sequencing (NGS) technology is increasingly utilized to identify therapeutic targets for patients with malignancy. This technology also has the capability to reveal the presence of constitutional genetic alterations, which may have significant implications for patients and their family members. Here we present the case of a 23 year old Caucasian patient with recurrent undifferentiated sarcoma who had NGS-based tumor analysis using an assay which simultaneously analyzed the entire coding sequence of 236 cancer-related genes (3769 exons) plus 47 introns from 19 genes often rearranged or...
Source: Familial Cancer - February 25, 2015 Category: Cancer & Oncology Source Type: research

Heterozygous germline mutations in NBS1 among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation
Abstract The purpose of the present study was to analyze genetic variations in the NBS1 gene and to evaluate the contribution of heterozygous NBS1 mutation to the risk of breast cancer among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation. We screened 235 non-BRCA1/2 Korean patients with high-risk breast cancer for NBS1 mutations. The entire NBS1 gene was sequenced using fluorescent conformation-sensitive capillary electrophoresis. In silico analysis of the NBS1 variants was performed using PolyPhen-2 and SIFT. The frequency of variants predicted to be deleterious by in silico analys...
Source: Familial Cancer - February 25, 2015 Category: Cancer & Oncology Source Type: research

Timing of risk reducing mastectomy in breast cancer patients carrying a BRCA1/2 mutation: retrospective data from the Dutch HEBON study
Abstract It is expected that rapid genetic counseling and testing (RGCT) will lead to increasing numbers of breast cancer (BC) patients knowing their BRCA1/2 carrier status before primary surgery. Considering the potential impact of knowing one’s status on uptake and timing of risk-reducing contralateral mastectomy (RRCM), we aimed to evaluate trends over time in RRCM, and differences between carriers identified either before (predictively) or after (diagnostically) diagnosis. We collected data from female BRCA1/2 mutation carriers diagnosed with BC between 1995 and 2009 from four Dutch university hospitals....
Source: Familial Cancer - February 21, 2015 Category: Cancer & Oncology Source Type: research

Polymorphisms of the XRCC1 gene and breast cancer risk in the Mexican population
Abstract The purpose of this case–control study was to evaluate the association of XRCC1 Arg194Trp and Arg399Gln polymorphisms with susceptibility to breast cancer (BC) in a Mexican population. We analysed DNA samples from 345 BC patients and 352 control subjects by polymerase chain reaction-restriction fragment length polymorphism. The frequency of the 399Gln allele was 23 % in controls and 29 % in patients [OR 1.38 (1.08–1.76); p = 0.01]; genotypes in controls were 60, 36, and 4 % for Arg/Arg, Arg/Gln, and Gln/Gln, respectively, while in patients they were 53, 36, and 11 ...
Source: Familial Cancer - February 18, 2015 Category: Cancer & Oncology Source Type: research

Large genomic rearrangements in the familial breast and ovarian cancer gene BRCA1 are associated with an increased frequency of high risk features
Abstract Large genomic rearrangements (LGRs) account for at least 10 % of the mutations in BRCA1 and 5 % of BRCA2 mutations in outbred hereditary breast and ovarian cancer (HBOC) families. Data from some series suggest LGRs represent particularly penetrant mutations. 1,034 index cases from HBOC families underwent comprehensive BRCA1 and BRCA2 mutation testing, including screening for LGRs. The personal and family history of 254 identified mutation carriers were compared based on mutation type. Thirty-six LGRs were detected; 32/122 (26 %) BRCA1 and 4/132 (3 %) BRCA2 mutations. High risk features...
Source: Familial Cancer - February 13, 2015 Category: Cancer & Oncology Source Type: research

Analysis of PALB2 in a cohort of Italian breast cancer patients: identification of a novel PALB2 truncating mutation
Abstract PALB2 gene is mutated in about 1–2 % of familial breast cancer as well as in 3–4 % of familial pancreatic cancer cases. Few studies have reported mutations in Italian patients with breast or pancreatic cancer. We evaluate the occurrence of PALB2 mutations in Italian patients affected with hereditary breast and ovarian cancers and define the pathological significance of the putative allelic variants. We recruited 98 patients (F = 93, M = 5) affected with breast and/or ovarian cancer, negative for mutations in BRCA1 and BRCA2 (BRCAX). Genomic DNA was isol...
Source: Familial Cancer - February 11, 2015 Category: Cancer & Oncology Source Type: research

Defective DNA mismatch repair activity is common in sebaceous neoplasms, and may be an ineffective approach to screen for Lynch syndrome
Abstract A subset of individuals with Lynch syndrome (LS) has a variant called Muir-Torre syndrome (MTS) where patients develop multiple sebaceous neoplasms. Absence of gene expression and microsatellite instability (MSI) have been welldocumented in LS neoplasms. It is unclear whether the presence of these abnormalities in isolated sebaceous neoplasms would indicate the likely presence of otherwise unsuspected LS or MTS. 164 specimens of sporadic cutaneous sebaceous neoplasms were obtained. IHC was performed for expression of the DNA mismatch repair (MMR) genes MSH2 and MLH1. A 5-marker mononucleotide repeat m...
Source: Familial Cancer - January 31, 2015 Category: Cancer & Oncology Source Type: research

The effect of oral 3,3′-diindolylmethane supplementation on the 2:16α-OHE ratio in BRCA1 mutation carriers
Abstract Hormonal exposures are known to influence breast cancer risk among women with a BRCA1 mutation. Thus, dietary factors that increase the 2-hydroxyestrone (OHE):16α-OHE ratio, a biomarker inversely related to breast cancer development, may also influence cancer risk. We conducted a dietary intervention study to evaluate the ability of 300 mg/day of 3,3′-diindolylmethane (DIM) to increase the urinary 2:16α-OHE ratio in 20 women with a BRCA1 mutation. BRCA1 mutation carriers (n = 15) were assigned to receive 300 mg/day of Rx Balance BioREsponse DIM for 4–6 week...
Source: Familial Cancer - January 23, 2015 Category: Cancer & Oncology Source Type: research