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 16, 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 6, 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 - January 1, 2017 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 - January 1, 2017 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 - January 1, 2017 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 - January 1, 2017 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 - January 1, 2017 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 - January 1, 2017 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 - January 1, 2017 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 30, 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 21, 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 17, 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 28, 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 28, 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 22, 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 21, 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 19, 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 19, 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 18, 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 15, 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 14, 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 12, 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 10, 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 10, 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 9, 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 9, 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 8, 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 - November 1, 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 31, 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 27, 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 25, 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 25, 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 22, 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 20, 2016 Category: Cancer & Oncology Source Type: research

Genetically diagnosed Birt –Hogg–Dubé syndrome and familial cerebral cavernous malformations in the same individual: a case report
AbstractWhen faced with an unusual clinical feature in a patient with a Mendelian disorder, the clinician may entertain the possibilities of either the feature representing a novel manifestation of that disorder or the co-existence of a different inherited condition. Here we describe an individual with a submandibular oncocytoma, pulmonary bullae and renal cysts as well as multiple cerebral cavernous malformations and haemangiomas. Genetic investigations revealed constitutional mutations inFLCN, associated with Birt –Hogg–Dubé syndrome (BHD) andCCM2, associated with familial cerebral cavernous malformati...
Source: Familial Cancer - October 8, 2016 Category: Cancer & Oncology Source Type: research

TP53 and CDKN1A mutation analysis in families with Li –Fraumeni and Li–Fraumeni like syndromes
In this study, we searched for mutations inTP53 in 39 probands from families with criteria for LFS/LFL. We also searched for mutations in the gene encoding the main mediator of p53 in cell cycle arrest,CDKN1A/p21, in all patients with no mutations inTP53. Eight probands carried germline disease-causing mutations inTP53: six missense mutations and two partial gene deletions. No mutations inCDKN1A coding region were detected.TP53 partial deletions in our cohort represented 25  % (2/8) of the mutations found, a much higher frequency than usually reported, emphasizing the need to search forTP53 rearrangements in patients ...
Source: Familial Cancer - October 6, 2016 Category: Cancer & Oncology Source Type: research

Modeling the dyadic effects of parenting, stress, and coping on parent –child communication in families tested for hereditary breast-ovarian cancer risk
AbstractGenetic testing forBRCA genes, associated with hereditary breast-ovarian cancer risk, is an accepted cancer control strategy.BRCA genetic testing has both medical and psychosocial implications for individuals seeking testing and their family members. However, promoting open and adaptive communication about cancer risk in the family is challenging for parents of minor children. Using prospective data collected from mothers undergoingBRCA genetic testing and their untested co-parents (N  = 102 parenting dyads), we examined how maternal and co-parent characteristics independently and conjointly influenced th...
Source: Familial Cancer - September 4, 2016 Category: Cancer & Oncology Source Type: research

Identification of a novel PMS2 alteration c.505C & gt;G (R169G) in trans with a PMS2 pathogenic mutation in a patient with constitutional mismatch repair deficiency
We describe the clinical and molecular features in the patient harboring this novel alteration c.505C>G, who meets clinical criteria for CMMRD and exhibits molecular evidence supporting a diagnosis of CMMRD. Although experimental validation is needed to confirm its pathogenicity,PMS2 c.505C>G likely has functional consequences that contributes to our patient ’s phenotype based on the patient’s clinical presentation, tumor studies, and bioinformatics analysis. (Source: Familial Cancer)
Source: Familial Cancer - September 4, 2016 Category: Cancer & Oncology Source Type: research

MSI detection and its pitfalls in CMMRD syndrome in a family with a bi-allelic MLH1 mutation
AbstractThe constitutional MisMatch Repair deficiency (CMMRD) syndrome is one of the inherited cancer predisposition syndromes. More than two-third patients belonging to a CMMRD family are diagnosed mainly in the first decade with brain cancers and/or hematological malignancies. This syndrome is due to bi-allelic germline mutations in genes of the MMR pathway (MLH1,MSH2,MSH6 orPMS2). Our family report begins with the index case presenting initially with a medulloblastoma, which was even the two relapses in complete remission, when she was diagnosed for an AML. She died after bone marrow transplantation from toxicity. The f...
Source: Familial Cancer - September 4, 2016 Category: Cancer & Oncology Source Type: research

BRCA testing within the Department of Veterans Affairs: concordance with clinical practice guidelines
AbstractGuideline-concordant cancer care is a priority within the Department of Veterans Affairs (VA). In 2009, the VA expanded its capacity to treat breast cancer patients within VA medical centers (VAMCs). We sought to determine whether male and female Veterans diagnosed with breast cancer received BRCA testing as recommended by the National Comprehensive Cancer Network (NCCN) guidelines on Genetic/Familial High-Risk Assessment in Breast and Ovarian Cancer (v. 1.2010 –1.2012). Using the 2011–2012 VA Central Cancer Registry and BRCA test orders from Myriad Genetics, we conducted a retrospective study. The outc...
Source: Familial Cancer - September 2, 2016 Category: Cancer & Oncology Source Type: research

Performance of Lynch syndrome predictive models in quantifying the likelihood of germline mutations in patients with abnormal MLH1 immunoexpression
AbstractLynch syndrome (LS) accounts for up to 4  % of all colorectal cancers (CRC). Detection of a pathogenic germline mutation in one of the mismatch repair genes is the definitive criterion for LS diagnosis, but it is time-consuming and expensive. Immunohistochemistry is the most sensitive prescreening test and its predictive value is very hig h for loss of expression ofMSH2,MSH6, and (isolated)PMS2, but not forMLH1. We evaluated if LS predictive models have a role to improve the molecular testing algorithm in this specific setting by studying 38 individuals referred for molecular testing and who were subsequently ...
Source: Familial Cancer - August 31, 2016 Category: Cancer & Oncology Source Type: research

A novel germline POLE mutation causes an early onset cancer prone syndrome mimicking constitutional mismatch repair deficiency
AbstractIn a 14-year-old boy with polyposis and rectosigmoid carcinoma, we identified a novelPOLE germline mutation, p.(Val411Leu), previously found as recurrent somatic mutation in ‘ultramutated’ sporadic cancers. This is the youngest reported cancer patient with polymerase proofreading-associated polyposis indicating thatPOLE mutation p.(Val411Leu) may confer a more severe phenotype than previously reportedPOLE andPOLD1 germline mutations. The patient had multiple caf é-au-lait macules and a pilomatricoma mimicking the clinical phenotype of constitutional mismatch repair deficiency. We hypothesize that...
Source: Familial Cancer - August 29, 2016 Category: Cancer & Oncology Source Type: research

Calculating the optimal surveillance for head and neck paraganglioma in SDHB -mutation carriers
This study included allSDHB mutation carriers who were followed at the Department of Endocrinology at the University Medical Center of Groningen. Kaplan –Meier curves were used to assess the penetrance. Poisson process was used to assess the optimal age to start surveillance and intervals. Ninety-oneSDHB-mutation carriers (38 men and 53 women) were included. Twenty-seven mutation carriers (30  %) had manifestations, with an overall penetrance 35 % at the age of 60 years. We calculated that optimal surveillance for HNPGL could start from an age of 27 years with an interval of 3.2 years. This s...
Source: Familial Cancer - August 29, 2016 Category: Cancer & Oncology Source Type: research

Hereditary leiomyomatosis and renal cell cancer syndrome: identification and clinical characterization of a novel mutation in the FH gene in a Colombian family
We report a Colombian family with HLRCC syndrome, with a novel mutation inFH gene (c.1349_1352delATGA) in which cutaneous leiomyomas have not been found, but other clinical manifestations such as type 2- papillary renal cell carcinoma, uterine leiomyomas and rare tumors were present. This investigation constitutes the first report of HLRCC syndrome in Colombia, and probably in Latin America. (Source: Familial Cancer)
Source: Familial Cancer - August 26, 2016 Category: Cancer & Oncology Source Type: research

Nevoid basal cell carcinoma syndrome caused by splicing mutations in the PTCH1 gene
AbstractNevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental defects and tumorigenesis such as medulloblastomas and basal cell carcinomas, caused by mutations of thepatched-1 (PTCH1) gene. To date, we have detected 73 mutations inPTCH1 and ten of them (14  %) were suspected splicing mutations. Eight out of the ten mutations were localized near the splice donor site. Five mutations were localized within the invariant GT-AG splice site, whereas the other five mutations occurred outside the invariant GT-AG site including the last exonic nucleotide. Whe n the transc...
Source: Familial Cancer - August 25, 2016 Category: Cancer & Oncology Source Type: research

Do women change their breast cancer mammogram screening behaviour after BRCA1/2 testing?
AbstractLittle is known about the change in mammograms use by women afterBRCA1/2 genetic testing. We compared the rate of bilateral mammograms after and prior toBRCA1/2 testing, according to test result. Information from the Quebec Health Insurance Board database was used to identify all registered mammograms delivered between May 1, 1998 and March 31, 2012 to a cohort of 396 unaffected French Canadian women tested forBRCA1/2 mutations. Mammograms incidence density ratios were calculated using the Cox proportional hazards model for repeated events.BRCA1/2 mutation carriers and women with an inconclusive result had more mam...
Source: Familial Cancer - August 23, 2016 Category: Cancer & Oncology Source Type: research

Characterization of BRCA1 and BRCA2 variants found in a Norwegian breast or ovarian cancer cohort
AbstractGermline mutations inBRCA1 andBRCA2 cause hereditary breast and ovarian cancer. Molecular screening of these two genes in patients with a family history of breast or ovarian cancer has revealed pathogenic variants as well as genetic variants of unknown significance (VUS). These VUS may cause a challenge in the genetic counseling process regarding clinical management of the patient and the family. We investigated 32 variants previously detected in 33 samples from patients with a family history of breast or ovarian cancer. cDNA was analyzed for alternative transcripts and selected missense variants located in the BRC...
Source: Familial Cancer - August 5, 2016 Category: Cancer & Oncology Source Type: research

Community attitudes towards a Jewish community BRCA1/2 testing program
AbstractAbout 2.5  % of the Ashkenazi-Jewish population carry one of three “founder” mutations inBRCA1 andBRCA2 (BRCA1/2). Currently, testing is offered to Jewish people with a personal and/or family history of breast and/or ovarian cancer; however less than half ofBRCA1/2 carriers within the Jewish population are aware of their family history. Population-based testing in other countries has shown to greatly increase the number of mutation carriers identified, compared to targeted testing of people with a family history. We aimed to assess the Australian Jewish community ’s attitudes towards such a p...
Source: Familial Cancer - August 1, 2016 Category: Cancer & Oncology Source Type: research

First description of mutational analysis of MLH1, MSH2 and MSH6 in Algerian families with suspected Lynch syndrome
In this study, we confirmed that MSH2 , MLH1, and MSH6 contribute to CRC susceptibility. This work represents the implementation of a diagnostic algorithm for the identification of Lynch syndrome patients in Algerian families. (Source: Familial Cancer)
Source: Familial Cancer - July 28, 2016 Category: Cancer & Oncology Source Type: research

Dilemmas in the management of screen-detected lesions in patients at high risk for pancreatic cancer
Abstract In 3–5 % of all cases of pancreatic ductal adenocarcinoma (PDAC), hereditary factors influence etiology. While surveillance of high-risk individuals may improve the prognosis, this study describes two very different outcomes in patients with screen-detected lesions. In 2000, a surveillance program of carriers of a CDKN2A/p16-Leiden-mutation consisting of annual MRI was initiated. Patients with a suspected pancreatic lesion undergo CT-scan and Endoscopic Ultrasound, and surgery is offered when a lesion is confirmed. In 2015, two patients with a screen-detected solid lesion were identified. In bo...
Source: Familial Cancer - July 12, 2016 Category: Cancer & Oncology Source Type: research