Expanding the genotype –phenotype spectrum in hereditary colorectal cancer by gene panel testing
AbstractHereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel-based approaches detecting both SNVs, indels and CNVs in the same assay. We applied a panel including 19 CRC susceptibility genes to 91 individuals of six phenotypic subgroups. Targeted NGS-based sequencing of the whole gene regions including introns of the 19 genes was used. The individuals had a family history of CRC or ha...
Source: Familial Cancer - March 19, 2017 Category: Cancer & Oncology Source Type: research

Supporting disclosure of genetic information to family members: professional practice and timelines in cancer genetics
AbstractDisclosure of genetic information within families is one of the longstanding questions under scrutiny in the field of genetics. Most of the probands entrusted with family disclosure succeed in this task, but there are still many problematic cases where it proves difficult. How can professionals help probands disclose this information? What levers can they activate to foster the diffusion of genetic information within families? In the context of a new legal framework concerning this question in France, this paper offers a comprehensive view of the process of genetic counselling in a cancer genetics department. Based...
Source: Familial Cancer - March 13, 2017 Category: Cancer & Oncology Source Type: research

Improved quality of risk-reducing salpingo-oophorectomy in Australasian women at high risk of pelvic serous cancer
AbstractObjectivesThe quality of risk-reducing salpingo-oophorectomy (RRSO) performed in Australasian women was previously reported to be suboptimal. Here we describe the quality of RRSO performed since 2008 in women enrolled in the same cohort and determine whether it has improved.DesignProspective cohort study of women at high risk of pelvic serous cancer (PSC) in kConFab. Eligible women had RRSO between 2008 and 2014 and their RRSO surgical and pathology reports were reviewed. “Adequate” surgery and pathology were defined as complete removal and paraffin embedding of all ovarian and extra-uterine fallopian t...
Source: Familial Cancer - March 10, 2017 Category: Cancer & Oncology Source Type: research

Prevalence of two BRCA1 mutations, 5382insC and 300T   & gt;  G, in ovarian cancer patients from Ukraine
AbstractOvarian cancer is the seventh most common cancer in women worldwide and the leading cause of gynecological malignant diseases-related deaths in women. The most significant risk factor for ovarian cancer is an inherited genetic mutation in one of two genes:breast cancer gene 1 (BRCA1) orbreast cancer gene 2 (BRCA2). The germline mutation c.5266dupC (also known as 5382insC or 5385insC) is the most common mutation among Slavic patients with breast and/or ovarian cancer. Missense mutation c.181T  >  G (also known as 300T >  G or p.C61G) is regarded as the founder change in many Central...
Source: Familial Cancer - March 10, 2017 Category: Cancer & Oncology Source Type: research

Lower gastrointestinal neuroendocrine neoplasms associated with hereditary cancer syndromes: a case series
We report the first case series of six patients with lower GI NENs who were diagnosed with hereditary GI cancer syndromes by germline testing. Two patients presented with poorly differentiated rectal neuroendocrine carcinoma (NECs) with colonic polyposis and were found to have Familial Adenomatous Polyposis and MYH-Associated Polyposis, respectively. Three patients with colorectal NENs (one well differentiated neuroendocrine tumor, NET, and two NECs), all of which displayed abnormal immunohistochemistry for mismatch repair proteins, were diagnosed with Lynch syndrome. One patient with a goblet cell carcinoid was diagnosed ...
Source: Familial Cancer - March 9, 2017 Category: Cancer & Oncology Source Type: research

Gastric tumours in FAP
AbstractGastric cancer is not a recognised extra-colonic manifestation of FAP, except in countries with a high prevalence of gastric cancer. Data regarding gastric adenomas in FAP are sparse. The aim of this study was to review the clinical characteristics of gastric tumours occurring within an FAP population from the largest European polyposis registry. All patients that developed a gastric adenoma or carcinoma were identified from a prospectively maintained registry database. The primary outcome measure was the occurrence of gastric adenoma or adenocarcinoma. Secondary outcomes includedAPC mutation, tumour stage, managem...
Source: Familial Cancer - March 6, 2017 Category: Cancer & Oncology Source Type: research

Patients with negative multi-gene panel testing: a back to the future paradox?
(Source: Familial Cancer)
Source: Familial Cancer - March 2, 2017 Category: Cancer & Oncology Source Type: research

High-risk individuals ’ perceptions of reproductive genetic testing for CDH1 mutations
AbstractReproductive genetic testing- PreNatal Diagnosis (PND) and Preimplantation Genetic Diagnosis (PGD) —forCDH1 mutations associated with Hereditary Diffuse Gastric Cancer (HDGC)is available in the UK. This qualitative interview study examined high-risk individuals ’ (n = 35) views ofCDH1 reproductive genetic testing. Interviewees generally regarded reproductive genetic testing as an acceptable form of HDGC risk management. However, some were concerned that their genetic risks required them to plan reproduction and anticipated difficulties communicating this to reproductive partners. Individua...
Source: Familial Cancer - February 14, 2017 Category: Cancer & Oncology Source Type: research

Gastric cancer in FAP: a concerning rise in incidence
We describe a recent, sudden increase in the incidence of gastric cancer in FAP. Seven of the ten cases were diagnosed in the last 20  months. Comparing our population to the SEER database for gastric cancer, the standardized incidence ratio is 140. All cases arose in patients with a carpeting of FGP and associated with large mounds of proximal gastric polyps. Nearly all patients were under upper endoscopic surveillance. This is  a concerning observation and reflects a change in the phenotypic presentation of FAP in Western patients. (Source: Familial Cancer)
Source: Familial Cancer - February 8, 2017 Category: Cancer & Oncology Source Type: research

A lesson from a reported pathogenic variant in Peutz-Jeghers syndrome: a case report
In this study, compound heterozygous variants ofLKB1, c.890G  >  A/ c.1062C >  G and del(exon1)/ c.1062C >  G, were identified in two sporadic Chinese PJS cases respectively. Although all these three variants had been related to the autosomal dominant PJS in previous studies, all evidences collected in this study including de novo data, segregation data, population data, in-silico data, and functional data indicated that del(exon1) and c.890G >  A are pathogenic in these two PJS families rather than c.1062C >  G. This finding would contrib...
Source: Familial Cancer - February 8, 2017 Category: Cancer & Oncology Source Type: research

Biallelic BRCA2 mutations in two black South African children with Fanconi anaemia
We present two cases of black South African patients with FA diagnosed with biallelicBRCA2 mutations and discuss the phenotypic consequences and implications for them and their families. Recognition of this severe end of the phenotypic spectrum of FA is critical in allowing for confirmation of the diagnosis as well as cascade screening and appropriate care of family members. (Source: Familial Cancer)
Source: Familial Cancer - February 8, 2017 Category: Cancer & Oncology Source Type: research

The association between prognosis of breast cancer and first-degree family history of breast or ovarian cancer: a systematic review and meta-analysis
AbstractWhether a positive family history of breast cancer or ovarian cancer (FHBOC) would affect the prognosis of breast cancer is still up for debate and further study. This meta-analysis was performed to clarify this issue. We reviewed two databases (PubMed and CNKI) for research articles published at any time from the inception of these databases to April 1, 2016 for articles detecting the impact of FHBOC on the prognosis of breast cancer. A meta-analysis was conducted to generated combined hazard ratios (HR) with 95% confidence intervals (CI) for overall survival (OS) and breast cancer-specific survival (BCSS). Eighte...
Source: Familial Cancer - February 6, 2017 Category: Cancer & Oncology Source Type: research

Universal screening for Lynch syndrome among patients with colorectal cancer: patient perspectives on screening and sharing results with at-risk relatives
This study indicates that patients are interested in being screened for LS and that sharing information on the risk of LS with at-risk family members is not a significant barrier. These findings provide novel insight into patient perspectives about screening for LS and can guide successful implementation of universal screening programs. (Source: Familial Cancer)
Source: Familial Cancer - February 6, 2017 Category: Cancer & Oncology Source Type: research

Correlation between germline mutations in MMR genes and microsatellite instability in ovarian cancer specimens
AbstractA high proportion of ovarian cancers from women who carry germline mutations in mismatch repair (MMR) genes demonstrate microsatellite instability (MSI). The utility of pre-screening ovarian cancer specimens for MSI to identify potential patients for germline screening for MMR mutations is uncertain. 656 women with malignant ovarian cancer underwent both MSI testing and germline mutation testing for large rearrangements in three MMR genes,MLH1, MSH2 andMSH6. Germline DNA sequencing data for the same genes was available. Among the 656 women, only four (0.6%) carried a clearly pathogenic MMR mutation. All four cancer...
Source: Familial Cancer - February 6, 2017 Category: Cancer & Oncology Source Type: research

Psychosocial morbidity in TP53 mutation carriers: is whole-body cancer screening beneficial?
We present preliminary psychosocial findings from 17 participants during their first 12  months on the trial. We found a significant reduction in participants’ mean anxiety from baseline to two weeks post WB-MRI (1.2, 95% CI 0.17 to 2.23 p = 0.025), indicative of some benefit. Emerging qualitative themes show most participants are emotionally supported and contained by the scree ning program and are motivated by their immediate concern about staying alive, despite being informed about the current lack of evidence around efficacy of screening for people with TP53 mutations in terms of cancer morbidi...
Source: Familial Cancer - January 24, 2017 Category: Cancer & Oncology Source Type: research

Efficacy versus effectiveness of clinical genetic testing criteria for BRCA1 and BRCA2 hereditary mutations in incident breast cancer
In conclusion, effectiveness of BRCA testing criteria was much lower tha n efficacy. Our results indicate that current testing criteria and procedures associated withBRCA1 andBRCA2 testing are insufficient. There is room for improvement of their efficacy, but even more so regarding effectiveness. Clinical BRCA testing routines need to be critically revised. (Source: Familial Cancer)
Source: Familial Cancer - January 23, 2017 Category: Cancer & Oncology Source Type: research

Baseline results from the UK SIGNIFY study: a whole-body MRI screening study in TP53 mutation carriers and matched controls
This study sought to investigate the role of one-off non-contrast whole-body MRI (WB MRI) in the screening of asymptomaticTP53 mutation carriers. 44TP53 mutation carriers and 44 population controls were recruited. Scans were read by radiologists blinded to participant carrier status. The incidence of malignancies diagnosed inTP53 mutation carriers against general population controls was calculated. The incidences of non-malignant relevant disease and irrelevant disease were measured, as well as the number of investigations required to determine relevance of findings. InTP53 mutation carriers, 6 of 44 (13.6, 95% CI 5.2 &nda...
Source: Familial Cancer - January 15, 2017 Category: Cancer & Oncology Source Type: research

Mutation screening of ACKR3 and COPS8 in kidney cancer cases from the CONFIRM study
AbstractAn apparently balanced t(2;3)(q37.3;q13.2) translocation that appears to segregate with renal cell carcinoma (RCC) has indicated potential areas to search for the elusive genetic basis of clear cell RCC. We applied Hi-Plex targeted sequencing to analyse germline DNA from 479 individuals affected with clear cell RCC for this breakpoint translocation and genetic variants in neighbouring genes on chromosome 2,ACKR3 andCOPS8. While only synonymous variants were found inCOPS8, one of the missense variants inACKR3:c.892C>T, observed in 4/479 individuals screened (0.8%), was predicted likely to damage ACKR3 function. I...
Source: Familial Cancer - January 5, 2017 Category: Cancer & Oncology Source Type: research

Exploring clinicians ’ attitudes about using aspirin for risk reduction in people with Lynch Syndrome with no personal diagnosis of colorectal cancer
AbstractRecent research has shown that aspirin reduces the risk of cancers associated with Lynch Syndrome. However, uncertainty exists around the optimal dosage, treatment duration and whether the benefits of aspirin as a risk-reducing medication (RRM) outweigh adverse medication related side-effects. Little is known about clinicians ’ attitudes, current practice, and perceived barriers to recommending aspirin as a RRM. To explore the attitudes of clinicians who discuss risk management options with patients with Lynch Syndrome towards using aspirin as a RRM. Clinicians were invited through professional organisations ...
Source: Familial Cancer - December 31, 2016 Category: Cancer & Oncology Source Type: research

Pancreas-sparing total duodenectomy for Spigelman stage IV duodenal polyposis associated with familial adenomatous polyposis: experience of 10 cases at a single institution
AbstractDuodenal cancer is a leading cause of death in patients with familial adenomatous polyposis (FAP). In patients with Spigelman ’s classification (SC) stage IV duodenal polyposis (DP), careful endoscopic surveillance by specialists or surgical intervention is mandatory. We herein report the surgical and pathological outcomes of FAP patients with SC stage duodenal polyposis undergoing pancreas-sparing total duodenectomy (PS TD), which has been rarely reported but seems optimal in such patients. PSTD and distal gastrectomy with Billroth-I type reconstruction in ten consecutive FAP patients with SC stage IV DP are...
Source: Familial Cancer - December 31, 2016 Category: Cancer & Oncology Source Type: research

Association of monoallelic MUTYH mutation among Egyptian patients with colorectal cancer
This study included 120 unrelated CRC Egyptian patients who were compared with 100 healthy controls from the same locality. For all individuals, DNA was genotyped forMUTYH p.Y179C and MUTYH p.G396D mutations using the T-ARMS-PCR technique. The frequencies of monoallelicMUTYH mutations showed a strong association with the increased risk of CRC among Egyptian patients compared with controls (12.5vs. 4.0  %, OR = 3.49, 95 % CI = 1.12–10.90,P = 0.03). Moreover, the frequency ofMUTYH p.Y179C mutation was noted to be significantly higher among CRC patients compared to controls rather...
Source: Familial Cancer - December 31, 2016 Category: Cancer & Oncology Source Type: research

Mutational analysis of TP53 gene in Tunisian familial hematological malignancies and sporadic acute leukemia cases
In this study, we have analyzed theTP53 gene by direct sequencing approach, in a panel of 18 Tunisian familial hematological malignancies cases including several forms of leukemia, lymphoma and myeloid syndrome and 22 cases of sporadic acute leukemia. In one familial case diagnosed with acute lymphoblastic leukemia, we reported an intronic substitution 559+1 G>A which may disrupt the splice site and impact the normal protein function. Most of the deleterious mutations (Arg158His; Pro282Trp; Thr312Ser) as classified by IARC data base, were commonly reported in ALL cases studied here. The cosegregation of the two variants...
Source: Familial Cancer - December 31, 2016 Category: Cancer & Oncology Source Type: research

Hereditary breast and ovarian cancer: successful systematic implementation of a group approach to genetic counselling
We report data for the Oct-2014–Aug-2015 period. 210 patients attended group counselling, up to eight simultaneously. We always fitted them within a 4-h time frame. Mean satisfaction score was 41/43. Kno wledge scores increased from 3.1/6 to 4.9/6 post-counselling (p value  
Source: Familial Cancer - December 31, 2016 Category: Cancer & Oncology Source Type: research

Frequency of germline PALB2 mutations among women with epithelial ovarian cancer
AbstractRecent studies suggest that mutations in the partner and localizer ofBRCA2 (PALB2) gene may predispose to ovarian cancer. It is of importance to clarify the prevalence and penetrance ofPALB2 mutations in an unselected population so that clinical recommendations for prevention can be implemented. We evaluated the prevalence of germline mutations inPALB2 among 1421 epithelial ovarian cancer patients and 4300 European controls from the National Heart, Lung, and Blood Institute ’s Exome Sequencing Project dataset. Clinical information was obtained from medical records and survival status was determined by linkage...
Source: Familial Cancer - December 31, 2016 Category: Cancer & Oncology Source Type: research

Factors associated with cancer worries in individuals participating in annual pancreatic cancer surveillance
AbstractIt is important to adequately and timely identify individuals with cancer worries amongst participants in a pancreatic ductal adenocarcinoma (PDAC) surveillance program, because they could benefit from psychosocial support to decrease distress. Therefore, the aim of this study was to assess both psychosocial and clinical factors associated with cancer worries. High-risk individuals participating in PDAC-surveillance were invited to annually complete a cancer worry scale (CWS) questionnaire which was sent after counseling by the clinical geneticist (T0), after intake for participation in PDAC-surveillance (T1), and ...
Source: Familial Cancer - December 31, 2016 Category: Cancer & Oncology Source Type: research

Novel and reported pathogenic variants in exon 11 of BRCA2 gene in a cohort of Sri Lankan young breast cancer patients
This study focused on young breast cancer patients who were screened for previously identified hotspot regions inBRCA2 gene. A total of 48 young breast cancer patients with family history of cancer and 25 healthy controls were studied. Direct sequencing was used to detect pathogenic and other sequence variants in the hotspot regions ofBRCA2 gene. Thirty-six sequence variants including seven pathogenic (c.2411_2412delAA/p.Glu804Valfs*2, c.2500_2501insG/p.Leu834Cysfs*4, c.3881T>G/p.Leu1294*, c.4768A>T/p.Lys1590*, c.5645C>G/p.Ser1882*, c.5747delC/p.His1916Phefs*3, c.6728C>T/p.Ser2243Phe) and two likely pathogenic ...
Source: Familial Cancer - December 29, 2016 Category: Cancer & Oncology Source Type: research

Identification of MSH2 inversion of exons 1 –7 in clinical evaluation of families with suspected Lynch syndrome
AbstractTraditional germline sequencing and deletion/duplication analysis does not detect Lynch syndrome-causing mutations in all individuals whose colorectal or endometrial tumors demonstrate mismatch repair (MMR) deficiency. Unique inversions and other rearrangements of the MMR genes have been reported in families with Lynch syndrome. In 2014, a recurrent inversion ofMSH2 exons 1 –7 was identified in five families suspected to have Lynch syndrome. We aimed to describe our clinical experience in identifying families with this specific inversion. Four probands whose Lynch syndrome-associated tumors demonstrated absen...
Source: Familial Cancer - December 20, 2016 Category: Cancer & Oncology Source Type: research

ATM mutations for surgeons
AbstractThe ataxia-telangiectasia mutated (ATM) gene encodes a protein kinase involved in DNA repair. Heterozygotic carriers are at an increased risk of developing breast cancer. As the use of genetic testing increases, identification of at-risk patients will also increase. The aim of this study is to review two cases of heterozygous ATM mutation carriers and review the literature to clarify the cancer risks and suggested management for breast surgeons who will be intimately involved in the care of these patients. (Source: Familial Cancer)
Source: Familial Cancer - December 16, 2016 Category: Cancer & Oncology Source Type: research

Four generations of SDHB-related disease: complexities in management
We present a case series of five SDHB mutation carriers over four generations from the same family to illustrate the complexities in management. (Source: Familial Cancer)
Source: Familial Cancer - November 27, 2016 Category: Cancer & Oncology Source Type: research

Embryonal rhabdomyosarcoma in a patient with a heterozygous frameshift variant in the DICER1 gene and additional manifestations of the DICER1 syndrome
This study describes a novel, heterozygous frameshiftDICER1 mutation in a patient, who is affected by different tumors of the DICER1-syndrome, including eRMS, CBME and suspected pleuropulmonary blastoma type I. By whole-exome sequencing of germline material using peripheral blood-derived DNA, we identified a single base pair duplication within theDICER1 gene (c.3405 dupA) that leads to a frameshift and results in a premature stop in exon 21 (p.Gly1136Arg). The metachronous occurrence of two unrelated tumor entities (eRMS and CBME) in a very young child within a short timeframe should have raised the suspicion of an underly...
Source: Familial Cancer - November 27, 2016 Category: Cancer & Oncology Source Type: research

Outcomes of retesting BRCA negative patients using multigene panels
This study demonstrates the clinical utility of multigene panels in a group of high risk individuals who previously tested negative for aBRCA1/2 mutation. This retesting approach revealed a pathogenic mutation in 11% of cases. Retesting led to significant change in clinical management in a majority of patients with actionable mutations (7 out of 11), as well as in those with mutations in genes which do not have specific management guidelines. (Source: Familial Cancer)
Source: Familial Cancer - November 21, 2016 Category: Cancer & Oncology Source Type: research

Truncation of the MSH2 C-terminal 60 amino acids disrupts effective DNA mismatch repair and is causative for Lynch syndrome
AbstractMissense variants of DNA mismatch repair (MMR) genes pose a problem in clinical genetics as long as they cannot unambiguously be assigned as the cause of Lynch syndrome (LS). To study such variants of uncertain clinical significance, we have developed a functional assay based on direct measurement of MMR activity in mouse embryonic stem cells expressing mutant protein from the endogenous alleles. We have applied this protocol to a specific truncation mutant ofMSH2 that removes 60 C-terminal amino acids and has been found in suspected LS families. We show that the stability of the MSH2/MSH6 heterodimer is severely p...
Source: Familial Cancer - November 20, 2016 Category: Cancer & Oncology Source Type: research

The hereditary nature of small cell carcinoma of the ovary, hypercalcemic type: two new familial cases
We report two new familial cases of SCCOHT. Affected members in both families and the associated tumours were found to carrySMARCA4 germline and somatic mutations, respectively, leading to loss of SMARCA4 protein expression in the tumours. Despite the rarity of familial SCCOHT, the high incidence of germline mutations is important to note, as without a family history of the disease, the hereditary nature of SCCOHT may be missed, especially if the mutation was inherited from the father or acquired de novo. The similarity between SCCOHT and rhabdoid tumours should be recognized, as infant carriers ofSMARCA4 mutations may be ...
Source: Familial Cancer - November 18, 2016 Category: Cancer & Oncology Source Type: research

Recurrent TP53 missense mutation in cancer patients of Arab descent
AbstractHereditary cancer comprises more than 10% of all breast cancer cases. Identification of germinal mutations enables the initiation of a preventive program that can include early detection or preventive treatment and may also have a major impact on cancer therapy. Several recurrent mutations were identified in theBRCA1/2 genes in Jewish populations however, in other ethnic groups in Israel, no recurrent mutations were identified to date. Our group established panel sequencing in cancer patients to identify recurrent, founder, and new mutations in the heterogeneous and diverse populations in Israel, We evaluated five ...
Source: Familial Cancer - November 18, 2016 Category: Cancer & Oncology Source Type: research

All in the family? Analyzing the impact of family history in addition to genotype on medullary thyroid carcinoma aggressiveness in MEN2A patients
In conclusion, a difference in age of MTC diagnosis among differentRET 634 kindreds was identified. In contrast, notable intra-familial variability in disease aggressiveness was observed. Based on these findings, we recommend counseling patients with codon 634 mutations that their MTC disease course cannot be predicted by that of their relatives. (Source: Familial Cancer)
Source: Familial Cancer - November 17, 2016 Category: Cancer & Oncology Source Type: research

Detection of false positive mutations in BRCA gene by next generation sequencing
This study critically evaluates the false positives in multiplex panels and suggests the need for careful analysis. We employed multiplex PCR basedBRCA1 andBRCA2 community Panel with ion torrent PGM machine for evaluation of these mutations. Out of all 41samples analyzed forBRCA1 andBRCA2 five were found with950_951 insA(Asn319fs) atChr13:32906565 position and one sample with1032_1033 insA(Asn346fs) atChr13:32906647, both being frame-shift mutations inBRCA2 gene.950_951 insA(Asn319fs) mutation is reported as pathogenic allele in NCBI dbSNP. On examination of IGV for all these samples, it was seen that both mutations had &l...
Source: Familial Cancer - November 14, 2016 Category: Cancer & Oncology Source Type: research

Identification of a rare germline NBN gene mutation by whole exome sequencing in a lung-cancer survivor from a large family with various types of cancer
AbstractNijmegen breakage syndrome is an autosomal recessive disorder caused by biallelic mutation inNBN gene. It is characterized by microcephaly, growth retardation, immuno-deficiency and cancer predisposition. The monoallelic carriers ofNBN gene are also reported to be at increased risk of developing various types of malignancy. We have investigated an individual with lung cancer from an extended family segregating different types of hereditary cancer over several generations, including lung, breast, ovarian, colon, prostate and renal cancers. By using next generation whole exome sequencing approach, we identified a rar...
Source: Familial Cancer - November 13, 2016 Category: Cancer & Oncology Source Type: research

Double germline mutations in APC and BRCA2 in an individual with a pancreatic tumor
We report on three brothers affected by pancreatic tumors, all due to different causes, including mutations associated with two different cancer predisposition syndromes in the same individual. In the index patient a germline mutation both in theAPC andBRCA2 gene was identified while one affected brother showed theBRCA2 mutation only and another brother is supposed to have developed pancreatic cancer due to multiple non-genetic risk factors. We outline the impact of a double germline mutation in two tumor predisposition genes in one individual and proven heterogeneity of multiple cases of pancreatic tumors in one family. W...
Source: Familial Cancer - November 11, 2016 Category: Cancer & Oncology Source Type: research

Analysis of a RECQL splicing mutation, c.1667_1667+3delAGTA, in breast cancer patients and controls from Central Europe
AbstractRECQL is a DNA helicase required for genomic stability. Two studies have recently identifiedRECQL as a novel breast cancer susceptibility gene. The most commonRECQL mutation, the 4  bp-deletion c.1667_1667+3delAGTA, was five-fold enriched in Polish breast cancer patients, but the exact magnitude of the risk is uncertain. We investigated two hospital-based breast cancer case–control series from Belarus and Germany, respectively, comprising a total of 2596 breast cancer patie nts and 2132 healthy females. The mutation was found in 9 cases and 6 controls, with an adjusted Odds Ratio 1.23 (95% CI 0.44–...
Source: Familial Cancer - November 9, 2016 Category: Cancer & Oncology Source Type: research

Cancer screening behaviors and risk perceptions among family members of colorectal cancer patients with unexplained mismatch repair deficiency
AbstractCommunication gaps in families with unexplained mismatch repair (MMR) deficiency (UMMRD) could negatively impact the screening behaviors of relatives of individual with UMMRD. We evaluated cancer risk perception, screening behaviors, and family communication among relatives of colorectal cancer (CRC) patients with UMMRD. Fifty-one family members of 17 probands with UMMRD completed a questionnaire about cancer risk perception, adherence to Lynch syndrome (LS) screening recommendations, and communication with relatives. Clinical data about the probands were obtained from medical records. Thirty-eight participants (78...
Source: Familial Cancer - November 9, 2016 Category: Cancer & Oncology Source Type: research

Colonoscopy in Lynch syndrome: the need for a new quality score
(Source: Familial Cancer)
Source: Familial Cancer - November 8, 2016 Category: Cancer & Oncology Source Type: research

DICER1 mutation and tumors associated with a familial tumor predisposition syndrome: practical considerations
AbstractThe familial tumor predisposition syndrome known asDICER1-pleuropulmonary blastoma (PPB) orDICER1 tumor predisposition syndrome was first described in 2009, and it involves an increased risk in the occurrence of various tumors, like cystic nephroma and PPB. Here is presented a girl with a cystic nephroma and two cystic lung lesions who was diagnosed years later with theDICER1 gene mutation. This mutation was also found in one of her parents. Thus, the screening for theDICER1 gene mutation may be important in children with certain/multiple tumors and their families. (Source: Familial Cancer)
Source: Familial Cancer - November 8, 2016 Category: Cancer & Oncology Source Type: research

Uptake of prenatal diagnostic testing for retinoblastoma compared to other hereditary cancer syndromes in the Netherlands
AbstractSince the 1980s the genetic cause of many hereditary tumor syndromes has been elucidated. As a consequence, carriers of a deleterious mutation in these genes may opt for prenatal diagnoses (PND). We studied the uptake of prenatal diagnosis for five hereditary cancer syndromes in the Netherlands. Uptake for retinoblastoma (Rb) was compared with uptake for Von Hippel –Lindau disease (VHL), Li–Fraumeni syndrome (LFS), familial adenomatous polyposis (FAP), and hereditary breast ovarian cancer (HBOC). A questionnaire was completed by all nine DNA-diagnostic laboratories assessing the number of independent mu...
Source: Familial Cancer - November 7, 2016 Category: Cancer & Oncology Source Type: research

Uptake of genetic counseling, genetic testing and surveillance in hereditary malignant melanoma ( CDKN2A ) in Norway
We describe whether they attend genetic counseling when invited, whether they want a mutation test after being counseled and whether they adhere to recommendations for surveillance. 66  % (95/144) of first-degree relatives to mutation carriers contacted us within the study period. 98 % (126/128) of all relatives who came for genetic counseling decided on genetic testing for their family’s mutation, and 93 % (66/71) of all mutation carriers wanted referral to yearly skin exami nations. Female relatives had a significantly higher uptake of genetic services compared to males, similar to the findings in fa...
Source: Familial Cancer - October 31, 2016 Category: Cancer & Oncology Source Type: research

Risk algorithms that include pathology adjustment for HER2 amplification need to make further downward adjustments in likelihood scores
AbstractTo assess the need for adjustment in the likelihood of germlineBRCA1/2 mutations in women with HER2+ breast cancers. We analysed primary mutation screens on women with breast cancer with unequivocal HER2 overexpression and assessed the likelihood ofBRCA1/BRCA2 mutations by age, oestrogen receptor status and Manchester score. Of 1111 primary BRCA screens with confirmed HER2 status only 4/161 (2.5%) of women with HER2 amplification had aBRCA1 mutation identified and 5/161 (3.1%) aBRCA2 mutation. The pathology adjusted Manchester score between 10 and 19% and 20%+ thresholds resulted in a detection rate of only 6.5 and...
Source: Familial Cancer - October 30, 2016 Category: Cancer & Oncology Source Type: research

Pain evaluation during gynaecological surveillance in women with Lynch syndrome
AbstractTo evaluate perceived pain during repetitive annual endometrial sampling at gynaecologic surveillance in asymptomatic women with Lynch syndrome (LS) over time and in addition to symptomatic women without LS, undergoing single endometrial sampling. In this prospective study, 52 women with LS or first degree relatives who underwent repetitive annual gynaecological surveillance including endometrial sampling of which 33 were evaluated twice or more and 50 symptomatic women without LS who had single endometrial sampling, were included. Pain intensity was registered with VAS scores. Differences in pain intensities betwe...
Source: Familial Cancer - October 26, 2016 Category: Cancer & Oncology Source Type: research

Attenuated polyposis of the large bowel: a morphologic and molecular approach
In conclusions, AFAP and MAP, the polyposis labeled by constitu tional mutations, represented about 25 % of all attenuated polyposis. Mutation-associated cases showed an earlier age of onset of polyps and were more frequent in the female sex. (Source: Familial Cancer)
Source: Familial Cancer - October 24, 2016 Category: Cancer & Oncology Source Type: research

BRCA1 allele-specific expression in genetic predisposed breast/ovarian cancer
AbstractGermline allele specific expression (ASE), resulting in a lowered expression of one of theBRCA1 alleles, has been described as a possible predisposition marker in Hereditary Breast or Ovarian Cancer (HBOC), usable for molecular diagnosis in HBOC. The main objective of this prospective case –control study was to compare the proportion of ASE between controls without familial history of breast or ovarian cancer, and HBOC cases withoutBRCA1 orBRCA2 deleterious mutation.BRCA1 ASE evaluated on three SNPs among controls and HBOC patients without deleterious mutation were assessed by pyrosequencing. The allelic rati...
Source: Familial Cancer - October 24, 2016 Category: Cancer & Oncology Source Type: research

A case of multiple gastrointestinal stromal tumors caused by a germline KIT gene mutation (p.Leu576Pro)
We report a case of a 21-year-old woman who presented to the emergency department with a 2-week history of asthenia, palpitations and upper gastrointestinal bleeding. After further clinical evaluation one gastric and two small bowel GISTs were diagnosed, which were surgically resected after neoadjuvant therapy with Imatinib. Diffuse hyperplasia of the interstitial cells of Cajal was also seen in the background gastric and small intestinal walls. Somatic mutational analysis of theKIT gene revealed a substitution at codon 576 in exon 11 (p.Leu576Pro) in all tumors and normal ileal mucosa. The germline nature of this mutation...
Source: Familial Cancer - October 21, 2016 Category: Cancer & Oncology Source Type: research

Cystic parathyroid glands in MEN1: A rare entity?
We report three cases of PCs in MEN1 patients affected by HPT, who underwent a total or subtotal parathyroidectomy with transcervical thymectomy. In our series, all three patients had an unsatisfactory postoperati ve course, at variance with the high percentage (over 90 %) of long-term success in MEN1 patients operated at our centre. One patient affected by cystic degeneration of all the four parathyroid glands reported persistent hypoparathyroidism, despite autografts of parathyroid tissue. For the other tw o cases, surgery failed to cure hyperparathyroidism, perhaps because of the presence of undetected ectopic para...
Source: Familial Cancer - October 19, 2016 Category: Cancer & Oncology Source Type: research