Risk management adherence following genetic testing for hereditary cancer syndromes: a Singaporean experience
AbstractAssessing adherence behavior among mutation carriers to cancer risk management guidelines is important for both service improvement and cost-effectiveness analyses, but such real-world data is often lacking. The present study aims to report adherence rates among mutation carriers in a recently established cancer genetics program in Singapore. We conducted a medical chart review of mutation carriers who had attended for genetic counseling and gathered data regarding risk management behavior, including cancer surveillance and/or risk-reducing surgery, and cancers subsequently detected. Of the 52 subjects included in ...
Source: Familial Cancer - January 24, 2018 Category: Cancer & Oncology Source Type: research

Mutations in SUFU and PTCH1 genes may cause different cutaneous cancer predisposition syndromes: similar, but not the same
AbstractMany cancer predisposition syndromes are preceded or accompanied by a range of typical skin signs. Gorlin syndrome is a rare multisystem inherited disorder which can predispose to basal cell carcinomas (BCCs), childhood medulloblastomas in addition to various developmental abnormalities; the majority of cases are due to mutations in thePTCH1 gene. Approximately 5% of cases have been attributed to a mutation in theSUFU gene. Certain phenotypic features have been identified as being more prevalent in individuals with aSUFU mutation such as childhood medulloblastoma, infundibulocystic BCCs and trichoepitheliomas. Rece...
Source: Familial Cancer - January 22, 2018 Category: Cancer & Oncology Source Type: research

Letter to the editor
(Source: Familial Cancer)
Source: Familial Cancer - January 12, 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 ...
Source: Familial Cancer - January 4, 2018 Category: Cancer & Oncology Source Type: research

The role of screening MRI in the era of next generation sequencing and moderate-risk genetic mutations
AbstractWith the advent of next-generation sequencing, the ability to rapidly analyze numerous genes simultaneously has led to the creation of large cancer gene panels. Some of these genes, likeBRCA1 andBRCA2, have been heavily researched and have well-established management guidelines. Other more newly established genes, likeATM, CHEK2, andPALB2, have previously had less robust research surrounding them which has limited the ability to create accurate risk estimates. With their inclusion on gene panels, there has been more pressure to produce management guidelines for patients discovered to carry pathogenic variants in th...
Source: Familial Cancer - January 1, 2018 Category: Cancer & Oncology Source Type: research

Haplotype analysis suggest that the MLH1 c.2059C   & gt;  T mutation is a Swedish founder mutation
AbstractLynch syndrome (LS) predisposes to a spectrum of cancers and increases the lifetime risk of developing colorectal- or endometrial cancer to over 50%. Lynch syndrome is dominantly inherited and is caused by defects in DNA mismatch-repair genesMLH1, MSH2, MSH6 orPMS2, with the vast majority detected inMLH1 andMSH2. Recurrent LS-associated variants observed in apparently unrelated individuals, have either arisen de novo in different families due to mutation hotspots, or are inherited from a founder (a common ancestor) that lived several generations back. There are variants that recur in some populations while also act...
Source: Familial Cancer - December 29, 2017 Category: Cancer & Oncology Source Type: research

Adaptation of couples living with a high risk of breast/ovarian cancer and the association with risk-reducing surgery
AbstractWomen who carryBRCA1/2 mutations have a significantly elevated risk for breast and ovarian cancer. The positive test result and subsequent decisions about risk reducing behaviors can evoke distress, anxiety and worry. Psychological adaptation, or the process of coming to terms with the implications of a health threat, is an understudied construct inBRCA1/2 carriers. Little is known about adaptation and how it relates to other aspects of living at high risk for cancer. Even less is understood about adaptation among partners ofBRCA1/2 carriers, and its relationship to adaptation in high risk individuals. Women at inc...
Source: Familial Cancer - December 5, 2017 Category: Cancer & Oncology Source Type: research

The importance of a well-structured pancreatic screening program for familial and hereditary pancreatic cancer
(Source: Familial Cancer)
Source: Familial Cancer - December 4, 2017 Category: Cancer & Oncology Source Type: research

Feasibility of endoscopic resection using bipolar snare for nonampullary duodenal tumours in familial adenomatous polyposis patients
AbstractThe management of duodenal and colorectal tumours is important in patients with familial adenomatous polyposis (FAP). Endoscopic resection (ER) should be carefully performed because the risk of complications during or after (ER) of nonampullary duodenal tumours is higher than that of stomach or colorectal lesions in general. Thus, we evaluated the feasibility of endoscopic resection using bipolar snare (ERB) for nonampullary duodenal tumours in FAP patients. Eleven FAP patients who underwent ERB for nonampullary duodenal tumours at our hospital between October 2013 and December 2016 were retrospectively analysed ba...
Source: Familial Cancer - November 30, 2017 Category: Cancer & Oncology Source Type: research

Metachronous colorectal cancer following segmental or extended colectomy in Lynch syndrome: a systematic review and meta-analysis
AbstractAround 5% of colorectal cancers are due to mutations within DNA mismatch repair genes, resulting in Lynch syndrome (LS). These mutations have a high penetrance with early onset of colorectal cancer at a mean age of 45  years. The mainstay of surgical management is either a segmental or extensive colectomy. Currently there is no unified agreement as to which management strategy is superior due to limited conclusive empirical evidence available. A systematic review and meta- analysis to evaluate the risk of metach ronous colorectal cancer (MCC) and mortality in LS following segmental and extensive colectomy. A s...
Source: Familial Cancer - November 30, 2017 Category: Cancer & Oncology Source Type: research

SNP association study in PMS2-associated Lynch syndrome
AbstractLynch syndrome (LS) patients are at high risk of developing colorectal cancer (CRC). Phenotypic variability might in part be explained by common susceptibility loci identified in Genome Wide Association Studies (GWAS). Previous studies focused mostly onMLH1, MSH2 andMSH6 carriers, with conflicting results. We aimed to determine the role of GWAS SNPs inPMS2 mutation carriers. A cohort study was performed in 507PMS2 carriers (124 CRC cases), genotyped for 24 GWAS SNPs, including SNPs at 11q23.1 and 8q23.3. Hazard ratios (HRs) were calculated using a weighted Cox regression analysis to correct for ascertainment bias. ...
Source: Familial Cancer - November 17, 2017 Category: Cancer & Oncology Source Type: research

Germline variant in MSX1 identified in a Dutch family with clustering of Barrett ’s esophagus and esophageal adenocarcinoma
AbstractThe vast majority of esophageal adenocarcinoma cases are sporadic and caused by somatic mutations. However, over the last decades several families have been identified with clustering of Barrett ’s esophagus and esophageal adenocarcinoma. This observation suggests that one or more hereditary factors may play a role in the initiation of Barrett’s esophagus and esophageal adenocarcinoma in these families. A Dutch family with clustering of Barrett’s esophagus and esophageal adenocarcinom a was identified. Normal DNA obtained from the proband diagnosed with Barrett’s esophagus was analyzed with ...
Source: Familial Cancer - November 13, 2017 Category: Cancer & Oncology Source Type: research

Universal determination of microsatellite instability using BAT26 as a single marker in an Argentine colorectal cancer cohort
AbstractMicrosatellite instability (MSI) is a hallmark tool for Lynch syndrome (LS) screening and a prognostic marker for sporadic colorectal cancer (CRC). In regions with limited resources and scarce CRC molecular characterization as South America, the implementation of universal MSI screening is under debate for both its purposes. We sought to estimate the frequency of BAT26 in colorectal adenocarcinomas and to determine associated clinical and histological features. Consecutive patients from a CRC registry were included. BAT26 determination was performed in all cases; if instability was found, immunohistochemistry (IHC)...
Source: Familial Cancer - November 11, 2017 Category: Cancer & Oncology Source Type: research

Association between miR-146a rs2910164 polymorphism and specific cancer susceptibility: an updated meta-analysis
This article will discuss the association between miR-146 rs2910164 polymorphism and cancer susceptibility in 38 independent case-control studies from 34905 individuals. The 38 case-control studies which were searched from PubMed were used for conducting a meta-analysis. There were 14670 cases and 20235 controls. ORs and 95% CIs were used for reflecting the strength of association between miR-146a rs2910164 polymorphism and cancer susceptibility. Subgroup analysis based on the cancer type, ethnicity and study designs. All analysis were performed by using the Stata 11.0 software. MiR-146a rs2910164 polymorphism and overall ...
Source: Familial Cancer - November 10, 2017 Category: Cancer & Oncology Source Type: research

Information and support needs of young women regarding breast cancer risk and genetic testing: adapting effective interventions for a novel population
In this report, we describe our adaptation of a previously-studied behavioral intervention for this population, utilizing a systematic approach outlined by the Centers for Disease Control and Prevention. First, we assessed the information needs and levels of distress in this population and correlates of this distress. These data then were used to inform the adaptation and piloting of a three-session telephone-based peer coaching intervention. One hundred young women (M age  = 25 years) who were first or second degree relatives ofBRCA1/2 mutation carriers participated. Sixty-three percent of the sample en...
Source: Familial Cancer - November 9, 2017 Category: Cancer & Oncology Source Type: research

Excluding Lynch syndrome in a female patient with metachronous DNA mismatch repair deficient colon- and ovarian cancer
AbstractPatients synchronously or metachronously presenting with ovarian and colon cancer can pose diagnostic challenges. A primary colon carcinoma can metastasize to one or both ovaries, two independent primary tumors can arise or an ovarian carcinoma can metastasize to the colon. Clinical and immunohistochemical characterization can aid the diagnosis. Recently, we reported that in difficult cases finding pathogenicAPC variants supports a colonic origin.In this case report we describe the clinical history of a female patient suspected for Lynch syndrome. She was diagnosed with a bilateral ovarian cancer at age 44, followe...
Source: Familial Cancer - November 9, 2017 Category: Cancer & Oncology Source Type: research

Genotype phenotype correlation in Asian Indian von Hippel –Lindau (VHL) syndrome patients with pheochromocytoma/paraganglioma
In conclusion, PCC/PGL are rare in patients with largeVHL deletions and if occur are most likely to be solitary. Patients with bilateral PCC or multifocal PCC/PGL are least likely to have largeVHL deletions. Our study also provides additional evidence for existence of the phenomenon of anticipation in VHL syndrome. (Source: Familial Cancer)
Source: Familial Cancer - November 9, 2017 Category: Cancer & Oncology Source Type: research

Correlation of IL-31 gene polymorphisms with susceptibility and clinical recurrence of bladder cancer
AbstractInterleukin-31 is a crucial cytokine triggering inflammation which could be one of the risk factors of tumors. However, data for correlation betweenIL-31 and tumors are limited. The purpose of our study was to discuss whether genetic polymorphisms ofIL-31 were associated with the susceptibility and clinical outcomes of bladder cancer. Our study enrolled 478 controls, 156 non-muscle-invasive bladder cancer (NMIBC) and 138 muscle-invasive bladder cancer (MIBC) patients. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping two single nucleotide polymorphisms (SNP...
Source: Familial Cancer - November 8, 2017 Category: Cancer & Oncology Source Type: research

Development of a high risk pancreatic screening clinic using 3.0  T MRI
We describe the establishment of a comprehensive multidisciplinary screening program using 3.0  T MRI. Criteria for screening included the presence of PC in: ≥ 2 first degree relatives (FDR), 1 FDR and 1 s degree relative (SDR), ≥ 3 any degree relatives (ADR), or any known hereditary cancer syndrome with increased PC risk. Imaging with 3.0 T MRI was performed routinely and endoscopic u ltrasound was used selectively. Screening was completed in 75 patients (pts). Hereditary cancer syndromes were present in 42 (56%) of the 75 pts: BRCA2 (18), ATM (8), BRCA1 (6), CDKN2A (4), PALB2 (3), Lynch (2), and Peut...
Source: Familial Cancer - November 3, 2017 Category: Cancer & Oncology Source Type: research

Cost-effectiveness evaluation of pre-counseling telephone interviews before face-to-face genetic counseling in cancer genetics
AbstractOne of the main challenges in cancer genetics is responding to the exponential demand for genetic counseling, especially in patients with breast and/or ovarian cancer. To address this demand, we have set up a new procedure, based on pre-genetic counseling telephone interviews (PTI) followed by routing of patients: D1, a PTI is scheduled within 14  days; D7–D14, genetic counselors perform a 20 min PTI in order to establish a pre-genetic counseling file, by collecting personal and family medical historyvia a structured questionnaire and; D10 –17, routing: pre-genetic counseling appointment files...
Source: Familial Cancer - October 27, 2017 Category: Cancer & Oncology Source Type: research

Phenotypic and genotypic heterogeneity of Lynch syndrome: a complex diagnostic challenge
AbstractLynch syndrome is the hereditary disorder that most frequently predisposes to colorectal cancer as well as predisposing to a number of extracolonic cancers, most prominently endometrial cancer. It is caused by germline mutations in the mismatch repair genes. Both its phenotype and genotype show marked heterogeneity. This review gives a historical overview of the syndrome, its heterogeneity, its genomic landscape, and its implications for complex diagnosis, genetic counseling and putative implications for immunotherapy. (Source: Familial Cancer)
Source: Familial Cancer - October 25, 2017 Category: Cancer & Oncology Source Type: research

Corrections to: Use of the BOADICEA Web Application in clinical practice: appraisals by clinicians from various countries
AbstractThe article “Use of the BOADICEA Web Application in clinical practice: appraisals by clinicians from various countries” written by Anne Brédart · Jean‑Luc Kop · Antonis C. Antoniou · Alex P. Cunningham · Antoine De Pauw ·Marc Tischkowitz · Hans Ehrencrona · Sylvie Dolbeault · Léonore Robieux · Kerstin Rhiem ·Douglas F. Easton · Peter Devilee · Dominique Stoppa‑Lyonnet· Rita Schmutlzer, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 16t...
Source: Familial Cancer - October 25, 2017 Category: Cancer & Oncology Source Type: research

Targeted massively parallel sequencing characterises the mutation spectrum of PALB2 in breast and ovarian cancer cases from Poland and Ukraine
This study is consistent with previous reports thatPALB2:c.509_510del andPALB2:c.172_175del are recurrent mutations associated with breast cancer predisposition in Polish women with a family history of the disease. Our study contributes to the accumulating evidence indicating thatPALB2 should be included in genetic testing for breast cancer susceptibility in these populations to enhance risk assessment and management of women at high-risk of developing breast cancer. This data could also contribute to ongoing work that is assessing the possible association between ovarian cancer risk andPALB2 mutations for which there is c...
Source: Familial Cancer - October 19, 2017 Category: Cancer & Oncology Source Type: research

Cancer risk management in Tasmanian women with BRCA1 and BRCA2 mutations
In this study we surveyed 193BRCA1/2 mutation carriers in the state of Tasmania to determine the uptake of cancer risk-reducing strategies and what factors might influence women ’s decisions in relation to both gynaecological and breast surgery. We observed that uptake of risk management strategies varied depending on the strength of the recommendation in the national guidelines. Uptake rates were>  90% for strategies which are strongly recommended, such as breast screening by MRI/mammogram and bilateral salpingo-oophorectomy, and were unaffected by demographic factors such as socio-economic disadvantage an...
Source: Familial Cancer - October 16, 2017 Category: Cancer & Oncology Source Type: research

Penetrance of a rare familial mutation predisposing to papillary thyroid cancer
We present a large family with NMTC in which we had previously described a culpable mutation. Participants provided their personal medical history and family history. The germline 4q32 A >  C mutation was detected in 34 of 68 tested individuals. Age-specific penetrance of thyroid cancer and benign thyroid disease was determined using the inverted Kaplan–Meier method of segregation analysis. Individuals who tested positive for the 4q32 mutation have a 68.9% (95% CI 46.5–88.7) ris k of developing thyroid cancer by age 70 and a 65.3% (95% CI 46.0–83.8) risk of developing benign thyroid disea...
Source: Familial Cancer - October 12, 2017 Category: Cancer & Oncology Source Type: research

Family history influences the tumor characteristics and prognosis of breast cancers developing during postmenopausal hormone therapy
AbstractLong term use of postmenopausal hormone therapy (HT) has been reported to increase breast cancer risk. On the other hand, observational studies suggest that breast cancers diagnosed during HT may have a more favorable prognosis. While family history is a risk factor for breast cancer, and genetic factors also influence prognosis, the role of family history in combination with HT use has been little studied. We investigated the relationship between HT, family history, and prognosis in 584 (267 exposed) familial and 952 (460 exposed) non-familial breast cancer cases, using three survival end points: death from breast...
Source: Familial Cancer - October 10, 2017 Category: Cancer & Oncology Source Type: research

Whole body magnetic resonance imaging (WB-MRI) and brain MRI baseline surveillance in TP53 germline mutation carriers: experience from the Li-Fraumeni Syndrome Education and Early Detection (LEAD) clinic
The objective of this study was to determine the diagnostic performance of whole body MRI (WB-MRI) and dedicated brain MRI screening as part of a comprehensive screening clinic called Li-Fraumeni Education and Early Detection (LEAD) at MD Anderson Cancer Center. Adult ( ≥21 year old) and pediatric (
Source: Familial Cancer - October 7, 2017 Category: Cancer & Oncology Source Type: research

Inherited DNA repair gene mutations detected by tumor next generation sequencing in urinary tract cancers
AbstractInterpretation of next-generation sequencing (NGS) of tumor tissue in patients with advanced Urinary Tract Cancer (UTC) is performed to guide treatment selection but may reveal pathogenic variants with germline implications. We identified three patients with UTC with unexpected germline DNA repair gene mutations. Specific testing for these was prompted by the detection of these mutations by tumor NGS. All three patients were nonsmokers with a strong family history of cancer. Two patients had upper tract UTC with age at diagnosis in the 40  s. One had a family history suggestive of hereditary breast/ovarian pre...
Source: Familial Cancer - September 18, 2017 Category: Cancer & Oncology Source Type: research

Mutations in context: implications of BRCA testing in diverse populations
This article discusses the potential impact of genetic testing on population health, focusing in particular on the mutational spectrum of breast cancer susceptibility genes in diverse populations. We identify the need for improved access to, and increased investment in, comprehensive cancer risk assessment and genetic testing as well as cancer control measures that take into account lifestyle, environmental, and social factors in understudied minority groups. (Source: Familial Cancer)
Source: Familial Cancer - September 16, 2017 Category: Cancer & Oncology Source Type: research

Germline mutations in lung cancer and personalized medicine
(Source: Familial Cancer)
Source: Familial Cancer - September 15, 2017 Category: Cancer & Oncology Source Type: research

International society for gastrointestinal hereditary tumours —InSiGHT
(Source: Familial Cancer)
Source: Familial Cancer - September 13, 2017 Category: Cancer & Oncology Source Type: research

An exploration of genotype-phenotype link between Peutz-Jeghers syndrome and STK11: a review
AbstractPeutz-Jeghers Syndrome (PJS) is an autosomal dominant hereditary polyposis syndrome. Clinical features include hamartomatous polyps, mucocutaneous pigmentation and an increased predisposition towards developing malignancy. Variants inSTK11, a tumour suppressor gene, located on Chromosome 19, predispose to PJS. Peutz-Jeghers Syndrome is associated with increased rates of malignancy, particularly gastrointestinal. However, PJS is also associated with increased gynaecological, testicular and thyroid papillary malignancy. Truncating variants inSTK11 are thought to predispose to a more severe phenotype. Phenotype severi...
Source: Familial Cancer - September 12, 2017 Category: Cancer & Oncology Source Type: research

Dental anomalies in pediatric patients with familial adenomatous polyposis
AbstractFamilial adenomatous polyposis patients often present with non-malignant extra-intestinal manifestations which include dental anomalies that may be evident prior to the appearance of the colonic adenomas. The aims of this study were to describe the prevalence and type of dental anomalies and the relationships between gene mutations and dental anomalies in these patients. Twenty-two pediatric familial adenomatous polyposis patients and 46 controls, who were age and gender matched participated. Familial adenomatous polyposis patient ’s had a dental examination with panoramic radiograph and medical record review...
Source: Familial Cancer - September 8, 2017 Category: Cancer & Oncology Source Type: research

Pancreatic neuroendocrine tumor in a patient with a TSC1 variant: case report and review of the literature
AbstractThe majority of pancreatic neuroendocrine tumors (PNETs) are sporadic while 10 –15% are attributable to one of several familial cancer syndromes. Hereditary forms are more commonly associated with Multiple Endocrine Neoplasia Type I and von Hippel Lindau Syndrome. However, patients with Tuberous sclerosis complex also have an increased incidence of PNETs. More often this has been reported in patients withTSC2 variants. In this case report, we summarize the literature regarding PNETs associated with Tuberous sclerosis complex, as well as present a case of a patient with aTSC1 variant and a PNET. This case high...
Source: Familial Cancer - September 8, 2017 Category: Cancer & Oncology Source Type: research

Discovery of mutations in homologous recombination genes in African-American women with breast cancer
AbstractAfrican-American women are more likely to develop aggressive breast cancer at younger ages and experience poorer cancer prognoses than non-Hispanic Caucasians. Deficiency in repair of DNA by homologous recombination (HR) is associated with cancer development, suggesting that mutations in genes that affect this process may cause breast cancer. Inherited pathogenic mutations have been identified in genes involved in repairing DNA damage, but few studies have focused on African-Americans. We screened for germline mutations in seven HR repair pathway genes in DNA of 181 African-American women with breast cancer, evalua...
Source: Familial Cancer - September 2, 2017 Category: Cancer & Oncology Source Type: research

Cancer patients ’ intentions towards receiving unsolicited genetic information obtained using next-generation sequencing
AbstractNext-generation sequencing (NGS) can be used to generate information about a patient ’s tumour and personal genome. This powerful diagnostic tool provides solicited and unsolicited hereditary genetic (risk) information that could have consequences for cancer patients and their quality of life. A well-defined approach for returning appropriate genetic risk information is needed in personalized cancer care. A qualitative design with semi-structured interviews was used. We conducted interviews with 24 Dutch patients with different types of cancer, both NGS-experienced and NGS-inexperienced, to learn their intent...
Source: Familial Cancer - August 29, 2017 Category: Cancer & Oncology Source Type: research

Sporadic endometrial adenocarcinoma with MMR deficiency due to biallelic MSH2 somatic mutations
We report t he case of a woman with an early-onset endometrial adenocarcinoma who was suspected to be affected with Lynch syndrome based on tumor dMMR phenotype (MSI associated with loss of expression of MSH2 and MSH6 proteins). After complete germline and somatic evaluations, this phenotype was eventually expl ained by twoMSH2 somatic mutations and the diagnosis of Lynch-like syndrome due to an unidentifiedMSH2 germline mutation was ruled out. Somatic mosaicism at low mutation rate was unlikely as no mutation was detected by DNA analysis from various tissue samples. Nevertheless, the three patient ’s children were t...
Source: Familial Cancer - August 17, 2017 Category: Cancer & Oncology Source Type: research

Immunohistochemical null-phenotype for mismatch repair proteins in colonic carcinoma associated with concurrent MLH1 hypermethylation and MSH2 somatic mutations
AbstractMicrosatellite instability, a well-established driver pathway in colorectal carcinogenesis, can develop in both sporadic and hereditary conditions via different molecular alterations in the DNA mismatch repair (MMR) genes. MMR protein immunohistochemistry (IHC) is currently widely used for the detection of MMR deficiency in solid tumors. The IHC test, however, can show varied staining patterns, posing challenges in the interpretation of the staining results in some cases. Here we report a case of an 80-year-old female with a colonic adenocarcinoma that exhibited an unusual “null” IHC staining pattern wi...
Source: Familial Cancer - August 17, 2017 Category: Cancer & Oncology Source Type: research

Mutational analysis of the RB1 gene and the inheritance patterns of retinoblastoma in Jordan
In conclusion, in addition to all bilateral RB patients in our cohort, 30% of unilateral cases showed germline mutation. Almost half (47%) of germline cases had inherited disease from affected (6%) parent or unaffected carrier (94%). Therefore molecular screening is critical for the genetic counseling regarding the risk for inherited RB in both unilatera l and bilateral cases including those with no family history. (Source: Familial Cancer)
Source: Familial Cancer - August 12, 2017 Category: Cancer & Oncology Source Type: research

A germline missense mutation in exon 3 of the MSH2 gene in a Lynch syndrome family: correlation with phenotype and localization assay
AbstractLynch syndrome is caused by germline mutations in any of the MisMatch Repair (MMR) genes. About 37% ofMSH2 variants are missense variants causing single amino-acid substitutions. Whether missense variants affect the normal function of MMR proteins is crucial both to provide affected families a more accurate risk assessment and to offer predictive testing to family members. Here we report one family, fulfilling both Amsterdam I and II criteria and Bethesda guidelines, referred to our center for genetic counselling. The proband and some of her relatives have been investigated for microsatellite instability (MSI), imm...
Source: Familial Cancer - August 7, 2017 Category: Cancer & Oncology Source Type: research

p53 signaling pathway polymorphisms, cancer risk and tumor phenotype in TP53 R337H mutation carriers
In conclusion, our results suggest that MDM2 SNP 309 may contribute to the LFL phenotype and also to an earlier age at diagnosis of ACC and BC cancer in carriers of the R337H founder mutation. (Source: Familial Cancer)
Source: Familial Cancer - July 29, 2017 Category: Cancer & Oncology Source Type: research

Pancreatic adenocarcinoma with a germline PTEN p.Arg234Gln mutation
AbstractA minor fraction of pancreatic ductal adenocarcinoma (PDAC) develops in association with germline mutations of the genes responsible for inherited cancer syndromes. However, the PDAC that has a germlinePTEN mutation has not received much attention. Genome-wide whole exome sequencing was performed on germline and somatic DNA from an 82-year-old woman who had developed a solid pancreatic cancer but did not show characteristic findings of PTEN hamartoma tumor syndromes (PHTS). Histology of the resected pancreatic tumor showed unique PDAC findings of primarily dendriform structures and dense fibrous tissue, accompanied...
Source: Familial Cancer - July 28, 2017 Category: Cancer & Oncology Source Type: research

Erratum to: A new hereditary colorectal cancer network in the Middle East and eastern Mediterranean countries to improve care for high-risk families
(Source: Familial Cancer)
Source: Familial Cancer - July 27, 2017 Category: Cancer & Oncology Source Type: research

Remarkable effects of imatinib in a family with young onset gastrointestinal stromal tumors and cutaneous hyperpigmentation associated with a germline KIT -Trp557Arg mutation: case report and literature overview
AbstractGastrointestinal stromal tumors (GISTs) occur mostly sporadically. GISTs associated with a familial syndrome are very rare and are mostly wild type forKIT and platelet-derived growth factor alpha (PDGFRA). To date 35 kindreds and 8 individuals have been described with GISTs associated with germlineKIT mutations. This is the third family described with a germline p.Trp557Arg mutation in exon 11 of theKIT gene. The effect of imatinib in patients harboring a germlineKIT mutation has been rarely described. Moreover, in some studies imatinib treatment was withheld considering the lack of evidence for efficacy of this tr...
Source: Familial Cancer - July 14, 2017 Category: Cancer & Oncology Source Type: research

A comparison of cosegregation analysis methods for the clinical setting
AbstractQuantitative cosegregation analysis can help evaluate the pathogenicity of genetic variants. However, genetics professionals without statistical training often use simple methods, reporting only qualitative findings. We evaluate the potential utility of quantitative cosegregation in the clinical setting by comparing three methods. One thousand pedigrees each were simulated for benign and pathogenic variants inBRCA1 andMLH1 using United States historical demographic data to produce pedigrees similar to those seen in the clinic. These pedigrees were analyzed using two robust methods, full likelihood Bayes factors (FL...
Source: Familial Cancer - July 10, 2017 Category: Cancer & Oncology Source Type: research

The spectrum of genetic variants in hereditary pancreatic cancer includes Fanconi anemia genes
AbstractApproximately 5 –10% of all pancreatic cancer patients carry a predisposing mutation in a known susceptibility gene. Since>90% of patients present with late stage disease, it is crucial to identify high risk individuals who may be amenable to early detection or other prevention. To explore the spectrum of hereditary pancreatic cancer susceptibility, we evaluated germline DNA from pancreatic cancer participants (n  = 53) from a large hereditary cancer registry. For those without a known predisposition mutation gene (n = 49), germline next generation sequencing was completed using...
Source: Familial Cancer - July 8, 2017 Category: Cancer & Oncology Source Type: research

Association of genetic variations in RTN4 3 ′-UTR with risk for clear cell renal cell carcinoma
AbstractNogo proteins play an important role in the apoptosis of cells, especially in tumor cells. The present study was conducted to evaluate whether the TATC (rs71682980) and CAA (rs34917480) insertion/deletion polymorphisms ofRTN4 3 ′-UTR are associated with clear cell renal cell carcinoma (ccRCC). These two polymorphisms were genotyped in 308 ccRCC patients and 466 healthy controls by polymerase chain reaction polyacrylamide gel electrophoresis (PCR-PAGE). Significantly reduced ccRCC risk was observed to be associated with t he TATCins/ins genotype carriers (Versus TATCdel/del: adjusted OR 0.53, 95% CI 0.32 &ndas...
Source: Familial Cancer - July 7, 2017 Category: Cancer & Oncology Source Type: research

Novel BRCA1 splice-site mutation in ovarian cancer patients of Slavic origin
We report a novel mutation LRG_292t1:c.4356delA,p.(Ala1453Glnfs*3) in the 12th exon ofBRCA1, in the splice site region near the donor site of intron 12. It is a frameshift mutation with the termination codon generated on the third amino acid position from the site of deletion. Human Splice Finder 3.0 and MutationTaster have assessed this variation as disease causing, based on the alteration of splicing, creation of premature stop codon and other potential alterations initiated by nucleotide deletion. Among the most important alterations are frameshift and splice site changes (score of the newly created donor splice site: 0...
Source: Familial Cancer - July 6, 2017 Category: Cancer & Oncology Source Type: research

A new hereditary colorectal cancer network in the Middle East and eastern mediterranean countries to improve care for high-risk families
AbstractColorectal cancer (CRC) has a very high incidence in the western world. Data from registries in the Middle East showed that the incidence of CRC is relatively low in these countries. However, these data also showed that CRC incidence has increased substantially over the past three decades and that a high proportion of cases are diagnosed at an early age (
Source: Familial Cancer - July 6, 2017 Category: Cancer & Oncology Source Type: research

Increased access to TP53 analysis through breast cancer multi-gene panels: clinical considerations
(Source: Familial Cancer)
Source: Familial Cancer - July 5, 2017 Category: Cancer & Oncology Source Type: research