Efficacy of paired tumor and germline testing in evaluation of patients with Lynch-like syndrome in a large integrated healthcare setting
AbstractPatients with mismatch repair (MMR) deficient colorectal cancer (CRC) without detectable germline pathogenic variants (PVs) or likely pathogenic variants (LPVs) in MMR genes are often labeled as Lynch-like syndrome (LLS). We sought to evaluate the efficacy of paired tumor and germline testing in risk stratification of patients with LLS in a large, community-based, integrated healthcare setting. Through the universal screening program for Lynch syndrome at Kaiser Permanente Northern California, we identified all patients with MMR deficient colorectal tumors without detectable germline PVs or LPVs between April 2011 ...
Source: Familial Cancer - November 20, 2020 Category: Cancer & Oncology Source Type: research

Early-onset malignant phyllodes breast tumor in a patient with germline pathogenic variants in NF1 and BRCA1 genes
In conclusion, we present the first case of a malignant phyllodes tumor of the breast in patient carrying pathogenic variants inNF1 andBRCA1. Further studies will be necessary to understand if the phyllodes histotype represents a very rare component of NF1-associated breast cancer. (Source: Familial Cancer)
Source: Familial Cancer - November 19, 2020 Category: Cancer & Oncology Source Type: research

Age at diagnosis of cancer in 185delAG BRCA1 mutation carriers of diverse ethnicities: tentative evidence for modifier factors
AbstractGermline pathogenic sequence variants (PSVs) inBRCA1 substantially increase risk for developing breast (BC) and ovarian cancer (OvC). Yet, incomplete penetrance suggests that modifier factors affect phenotypic expression of mutantBRCA1 alleles. Analysis of identicalBRCA1 PSV carriers of diverse ethnicities may provide further evidence for modifier factors. Female carriers of the 185delAGBRCA1 PSV identified through high-risk clinics in Israel, and Manchester England from 1998-2018 were eligible. Data were retrieved from patients records and confirmed (in Israel) by cross referencing with the Israeli National Cancer...
Source: Familial Cancer - November 9, 2020 Category: Cancer & Oncology Source Type: research

Identification and management of Lynch syndrome in the Middle East and North African countries: outcome of a survey in 12 countries
ConclusionThe identification and management of LS in ME/NA countries are suboptimal and as a result most LS families in the region remain undetected. Future efforts should focus on increasing awareness of LS amongst both the general population and doctors, and on the improvement of the infrastructure in these countries. (Source: Familial Cancer)
Source: Familial Cancer - October 24, 2020 Category: Cancer & Oncology Source Type: research

Frequency and spectrum of mutations across 94 cancer predisposition genes in African American women with invasive breast cancer
AbstractAfrican American women are at increased risk of being diagnosed at a young age and/or with triple negative breast cancer, both factors which are included in current guidelines for identifying women who may benefit from genetic testing. Commercial breast cancer predisposition genetic panels, based largely on data derived from women of European ancestry, may not capture the full spectrum of cancer predisposition genes associated with breast cancer in African American women. Between 2001 and 2018, 488 unselected African American women with invasive breast cancer enrolled in the Clinical Breast Care Project. National C...
Source: Familial Cancer - October 21, 2020 Category: Cancer & Oncology Source Type: research

A novel germline variant in RET gene resulting in an additional cysteine in a family with familial medullary thyroid carcinoma
We describe a novel c.1765A >  T variant ofRET proto-oncogene in a family with medullary thyroid carcinoma (MTC) that predicts the creation of an additional cysteine p.(Ser589Cys) in the cysteine-rich domain. In this site only three other punctual variants have been described, giving rise to extra cysteines. We have characterized the clinical phenotype of this family. The index case was a 79-year-old woman with MTC in both thyroid lobes. This variant co-segregates in this family in four affected members. One member was operated on at 31  years of age and already presented MTC, indicating that prophyla...
Source: Familial Cancer - October 21, 2020 Category: Cancer & Oncology Source Type: research

The role of TP53 pathogenic variants in early-onset HER2-positive breast cancer
AbstractBreast cancer is the most frequent event in Li-Fraumeni syndrome associated with germlineTP53 variants. Some studies have shown that breast cancers in women with Li-Fraumeni syndrome are commonly HER2-positive, suggesting thatHER2 amplification or over-expression in a young woman may be a useful criterion to test for germline variants in theTP53 gene. We assessed the prevalence of germlineTP53 variants by Sanger sequencing or next-generation sequencing in 149 women with HER2-positive breast cancer diagnosed until age 40. The pattern ofHER2 amplification was evaluated with dual-probe FISH in a subset of breast carci...
Source: Familial Cancer - October 14, 2020 Category: Cancer & Oncology Source Type: research

Discordant DNA mismatch repair protein status between synchronous or metachronous gastrointestinal carcinomas: frequency, patterns, and molecular etiologies
This study aims at examining the frequency, patterns and molecular etiologies of such inter-tumoral MMR discordances. We analyzed a cohort of 2159 colorectal cancer (CRC) patients collected over a 5-year period and found that 1.3% of the patients (27/2159) had  ≥ 2 primary CRCs, and 25.9% of the patients with ≥ 2 primary CRCs (7/27) exhibited inter-tumoral MMR discordance. We then combined the seven MMR-discordant CRC patients with three additional MMR-discordant GIT carcinoma patients and evaluated their discordant patterns and associated mol ecular abnormalities. The 10 patients consiste...
Source: Familial Cancer - October 9, 2020 Category: Cancer & Oncology Source Type: research

FRAMe: Familial Risk Assessment of Melanoma —a risk prediction tool to guide CDKN2A germline mutation testing in Australian familial melanoma
AbstractGermline mutations inCDKN2A greatly increase risk of developing cutaneous melanoma. We have constructed a risk prediction model, Familial Risk Assessment of Melanoma (FRAMe), for estimating the likelihood of carrying a heritableCDKN2A mutation among Australian families, where the prevalence of these mutations is low. Using logistic regression, we analysed characteristics of 299 Australian families recruited through the Sydney site of GenoMEL (international melanoma genetics consortium) with at least three cases of cutaneous melanoma (in situ and invasive) among first-degree blood relatives, for predictors of the pr...
Source: Familial Cancer - September 28, 2020 Category: Cancer & Oncology Source Type: research

New surveillance guidelines for Li-Fraumeni and hereditary TP53 related cancer syndrome: implications for germline TP53 testing in breast cancer
(Source: Familial Cancer)
Source: Familial Cancer - September 27, 2020 Category: Cancer & Oncology Source Type: research

Patient reported experiences following laparoscopic prophylactic bilateral salpingo-oophorectomy or salpingectomy in an ambulatory care hospital
The objective of this study was to examine whether women undergoing prophylactic laparoscopic BSO felt they were adequately informed about post-operative outcomes. A telephone interview was conducted among 46 women undergoing laparoscopic BSO to collect detailed information regarding surgical outcomes, complications, symptoms, and time to return to daily activities. The average age at surgery was 45.0  years (range 34–66) and 67% of women underwent BSO prior to age 50. The mean reported hospital stay was 7.2 h (range 4–12 h) and at time of discharge, 78% of the women felt well enough to go home. ...
Source: Familial Cancer - September 22, 2020 Category: Cancer & Oncology Source Type: research

Quantitative evaluation of MSI testing using NGS detects the imperceptible microsatellite changed caused by MSH6 deficiency
AbstractMicrosatellite instability (MSI) is an effective biomarker for diagnosing Lynch syndrome (LS) and predicting the responsiveness of cancer therapy. MSI testing is conventionally performed by capillary electrophoresis, and MSI status is judged by visual assessment of allele size change. Here, we attempted to develop a quantitative evaluation model of MSI using next-generation sequencing (NGS). Microsatellite markers were analyzed in tumor and non-tumor tissues of colorectal cancer patients by NGS after a single multiplex polymerase chain reaction amplification. The read counts corresponding to microsatellite loci len...
Source: Familial Cancer - September 18, 2020 Category: Cancer & Oncology Source Type: research

Prevalence of pancreaticobiliary cancers in Irish families with pathogenic BRCA1 and BRCA2 variants
This study assessed the prevalence, age and gender distribution of PDAC/BTC cases in families known to carry aBRCA1/2 PV compared to those of the Irish population. A review of all families referred to a national genetics clinic from 09/11/1997 to 01/06/2018 was performed. The BOADICEA algorithm was used to estimate the probability that an untested relative of a knownBRCA1/2 PV carrier with PDAC was a carrier. We reviewed 3252 family pedigrees, 1193 contained a proband who underwent testing forBRCA1/2 based on Manchester score  ≥ 15. Among 128BRCA2 PV-positive families, 27 (21%) contained a 1st/2nd/3rd-degr...
Source: Familial Cancer - September 11, 2020 Category: Cancer & Oncology Source Type: research

Worldwide variation in lynch syndrome screening: case for universal screening in low colorectal cancer prevalence areas
AbstractTo perform a systematic assessment of universal Lynch syndrome (LS) screening yield in colorectal cancer (CRC) patients around the world. Universal screening for LS is recommended in all CRC patients. However, the variation in yield of LS screening in the setting of significant global variation in CRC prevalence is unknown. A systematic review of articles in the MEDLINE database was performed to identify studies performing universal screening for LS. All cases with microsatellite instability (MSI-H) or missing one or more proteins on immunohistochemistry (IHC) were considered screening positive. The overall pooled ...
Source: Familial Cancer - September 10, 2020 Category: Cancer & Oncology Source Type: research

Genetic testing and surveillance in infantile myofibromatosis: a report from the SIOPE Host Genome Working Group
This report provides a brief review of the clinical manifestations and genetics of IM and summarizes our interdisciplinary recommendations. (Source: Familial Cancer)
Source: Familial Cancer - September 4, 2020 Category: Cancer & Oncology Source Type: research

Clinical phenotypes combined with saturation genome editing identifying the pathogenicity of BRCA1 variants of uncertain significance in breast cancer
AbstractCharacterizing the pathogenicity ofBRCA1 variants of uncertain significance (VUSs) is a major bottleneck in clinical management ofBRCA1-associated breast cancer. Saturation genome editing (SGE) was recently reported as an innovative laboratory-based approach to assess the pathogenicity ofBRCA1 variants. We combined clinical phenotypes and SGE score to identify the pathogenicity ofBRCA1 VUSs detected in a cohort of 8,085 breast cancer patients. According to SGE function score, 33 out of 144BRCA1 VUSs detected were classified into “loss of function” (n = 13), “intermediate” (n&th...
Source: Familial Cancer - August 16, 2020 Category: Cancer & Oncology Source Type: research

Is a colorectal neoplasm diagnosis a trigger to change dietary and other lifestyle habits for persons with Lynch syndrome? A prospective cohort study
AbstractA cancer diagnosis is suggested to be associated with changes in dietary and lifestyle habits. Whether this applies to persons with familial cancer, such as Lynch syndrome (LS) is unknown. We investigated whether a colorectal neoplasm (CRN) diagnosis in persons with LS is associated with changes in dietary and lifestyle habits over time. We used data of confirmed LS mutation carriers from the GEOLynch study, a prospective cohort study. Information on dietary intake and lifestyle habits was collected with a validated semi-quantitative food frequency questionnaire and a general questionnaire administered at baseline ...
Source: Familial Cancer - August 7, 2020 Category: Cancer & Oncology Source Type: research

Recent advances in Lynch syndrome
(Source: Familial Cancer)
Source: Familial Cancer - August 7, 2020 Category: Cancer & Oncology Source Type: research

Barriers and facilitators to CDH1 carriers contemplating or undergoing prophylactic total gastrectomy
This study examined factors related to decision-making about PTG in three groups of individuals who: (1) underwent PTG immediately after receiving genetic testing results; (2) delayed PTG by ≥ 1 year or; (3) declined PTG. Participants were recruited from a familial gastric cancer registry at a tertiary care hospital. Patients withCDH1 pathogenic or likely pathogenic variants who contemplated and/or underwent PTG were eligible. 24 individuals contemplated PTG: 9 had immediate surgery (within a year), 8 delayed surgery, and 7 declined surgery. Data on PTG barriers and facilitators were obtained on all particip...
Source: Familial Cancer - August 4, 2020 Category: Cancer & Oncology Source Type: research

Characterizing germline APC and MUTYH variants in Ashkenazi Jews compared to other individuals
AbstractGermline variants in theAPC andMUTYH genes contribute to colorectal cancer (CRC) and adenoma risk, though may occur with varying frequencies in individuals of different ancestries. The aim of this study was to evaluate the prevalence ofAPC, monoallelicMUTYH and biallelicMUTYH germline variants in Ashkenazi Jewish (AJ) and Other Ancestry (OA) individuals with colorectal adenomas. We studied 7225 individuals with colorectal adenomas who had germlineAPC andMUTYH testing at a commercial laboratory. Cross-sectional medical history data were extracted from provider-completed test requisition forms. We performed bivariate...
Source: Familial Cancer - August 2, 2020 Category: Cancer & Oncology Source Type: research

Recent advances in Lynch syndrome: response to M øller et al.
(Source: Familial Cancer)
Source: Familial Cancer - August 2, 2020 Category: Cancer & Oncology Source Type: research

Multiple primary cancers (renal papillary, lymphoma and teratoma) and hepatic cysts in association with a pathogenic germline mutation in the MET gene
AbstractActivating germline mutations of theMET gene are associated with hereditary papillary renal cancer. This a very rare autosomal dominant condition, which is usually considered not to display a phenotype of multiple types of malignancy. However, this report describes the case of a man who has been affected with testicular teratoma, diffuse large B-cell lymphoma and multiple hepatic cysts, as well as multiple papillary renal cancers. There is good supporting evidence for roles of over-expression/activity of the HGF/MET ligand-receptor in development of these tumours, raising the possibility of other increased cancer r...
Source: Familial Cancer - July 19, 2020 Category: Cancer & Oncology Source Type: research

Complete response of hereditary leiomyomatosis and renal cell cancer (HLRCC)-associated renal cell carcinoma to nivolumab and ipilimumab combination immunotherapy by: a case report
We report an aggressive RCC case in a 49-year-old man. Nine weeks after undergoing a total nephroureterectomy of the right kidney, he had a metastasectomy at port site. Within 14 weeks of the initial surgery, multiple recurrent tumors developed in the right retroperitoneal space. The pathological diagnosis was FH-deficient RCC. Genetic testing identified a heterozygous germline mutation ofFH (c.641_642delTA), which confirmed the diagnosis of HLRCC-RCC. He received combination therapy with the immune checkpoint inhibitors (ICIs) nivolumab and ipilimumab as the first-line therapy. After 31 weeks of ICI treatment, a complete ...
Source: Familial Cancer - July 14, 2020 Category: Cancer & Oncology Source Type: research

Report of the fifth meeting of the European Consortium 'Care for CMMRD' (C4CMMRD), Leiden, The Netherlands, July 6th 2019
(Source: Familial Cancer)
Source: Familial Cancer - July 1, 2020 Category: Cancer & Oncology Source Type: research

Improving primary care identification of familial breast cancer risk using proactive invitation and decision support
This study demonstrated proactive risk assessment in primary care enables accurate identification of women, including many younger women, at increased risk of breast cancer. To improve generalisability across the population, more active me thods of engagement need to be explored.Trial registration: CRUK Clinical Trials  Database 11779. (Source: Familial Cancer)
Source: Familial Cancer - June 10, 2020 Category: Cancer & Oncology Source Type: research

Chemoprevention in familial adenomatous polyposis: past, present and future
AbstractFamilial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome characterized by colorectal adenomas and a near 100% lifetime risk of colorectal cancer (CRC). Prophylactic colectomy, usually by age 40, is the gold-standard therapy to mitigate this risk. However, colectomy is associated with morbidity and fails to prevent extra-colonic disease manifestations, including gastric polyposis, duodenal polyposis and cancer, thyroid cancer, and desmoid disease. Substantial research  has investigated chemoprevention medications in an aim to prevent disease progression, postponing the need for colectomy ...
Source: Familial Cancer - June 7, 2020 Category: Cancer & Oncology Source Type: research

Prospective observational data informs understanding and future management of Lynch syndrome: insights from the Prospective Lynch Syndrome Database (PLSD)
AbstractThe Prospective Lynch Syndrome Database (PLSD) has been developed as an international, multicentre, prospective, observational study that aims to provide age and organ-specific cancer risks according to gene and gender, estimates of survival after cancer and information on the effects of interventions. Recent reports from PLSD provided improved estimates of cancer risks and survival and showed that different time intervals between surveillance colonoscopies did not affect the incidence, stage or prognosis of colorectal cancer. The PLSD reports suggest that current management guidelines for Lynch syndrome should be ...
Source: Familial Cancer - June 7, 2020 Category: Cancer & Oncology Source Type: research

Germline variants discovered in lymphoma patients undergoing tumor profiling: a case series
AbstractClinical tumor sequencing protocols often depend on obtaining germline DNA from patients to aid in the identification of de novo variants in the tumor, and therefore come with the possibility for the incidental discovery of germline variants. Ninety-one adult patients with lymphoma were consented and enrolled in MIONCOSEQ, an IRB-approved tumor profiling protocol that utilizes an exome sequencing platform. Charts were retrospectively reviewed for germline variants from sequencing results, personal and/or family history of cancer and genetic counseling referral. After review of the 91 lymphoma cases, seven (8%) case...
Source: Familial Cancer - June 5, 2020 Category: Cancer & Oncology Source Type: research

Two cases of somatic STK11 mosaicism in Danish patients with Peutz –Jeghers syndrome
We report two Danish patients withSTK11 mosaicism detected in blood when using Next-Generation Sequencing. This is only the sixth and seventh patient reported in the literature, and we compare phenotypes of the reported cases. The results indicate thatSTK11 mosaicism is more frequent than anticipated and highlight that mosaicism should be considered in patients with clinical suspicion of PJS or patients fulfilling the diagnostic criteria. (Source: Familial Cancer)
Source: Familial Cancer - June 5, 2020 Category: Cancer & Oncology Source Type: research

Constitutional mosaicism for a BRCA2 mutation as a cause of early-onset breast cancer
We report on a breast cancer patient with constitutional somatic mosaicism of aBRCA2 mutation.BRCA2 mutation c.9294C>G, p.(Tyr3098Ter) was detected in 20% of reads in DNA extracted from peripheral blood using next-generation sequencing (NGS). TheBRCA2 mutation was subsequently observed at similar levels in normal breast tissue, adipose tissue, normal right fallopian tube tissue and ovaries of the patient, suggesting that this mutation occurred early in embryonic development. This is the first case to report constitutional mosaicism for aBRCA2 mutation and shows thatBRCA2 mosaicism can underlie early-onset breast cancer....
Source: Familial Cancer - May 27, 2020 Category: Cancer & Oncology Source Type: research

Small fraction of testicular cancer cases may be causatively related to CHEK2 inactivating germ-line mutations: evidence for somatic loss of the remaining CHEK2 allele in the tumor tissue
AbstractA recent study suggested a role ofCHEK2 loss-of-function germ-line pathogenic variants in the predisposition to testicular cancer (TC) (AlDubayan et al. JAMA Oncol 5:514 –522, 2019). We attempted to validate this finding relying on the high population frequency of recurrentCHEK2 pathogenic variants in Slavic populations.CHEK2 pathogenic alleles (c.1100delC (p.Thr367Metfs); del5395 [del ex9-10]; IVS2  + 1G >  A [c.444 + 1G >  A]) were detected in 7/280 (2.5%) TC patients vs. 3/424 (0.7%) healthy men and 6/1007 (0.6%) healthy women [OR 4.0 (95% CI 1....
Source: Familial Cancer - May 25, 2020 Category: Cancer & Oncology Source Type: research

Low accuracy of self-reported family history of melanoma in high-risk patients
AbstractFamily history of melanoma is a major melanoma risk factor. However, self-reported family histories for some cancers, including melanoma, are commonly inaccurate. We used a unique database, the Utah Population Database (UPDB), as well as the Utah Cancer Registry to determine the accuracy of self-reported family history of melanoma in a large cohort of high-risk patients. Patient charts were reviewed and compared to records in the UPDB and the UCR to confirm personal and family history of melanoma in 1780 patients enrolled in a total body photography monitoring program. Self-reported family history of melanoma in fi...
Source: Familial Cancer - May 20, 2020 Category: Cancer & Oncology Source Type: research

Women ’s responses and understanding of polygenic breast cancer risk information
This study aimed to explore women ’s experience receiving their personalised polygenic risk score (PRS) and compare responses of women at different levels of polygenic risk. Eligible participants were affected and unaffected women from families clinically assessed to be at high risk for breast cancer who had received their persona lised PRS as part of the Variants in Practice Psychosocial Study (ViPPs). In-depth semi-structured interviews were conducted with 21 women (mean age 53.4 years) up to four weeks after receiving their PRS. Interviews were transcribed verbatim and analysed using thematic analysis. Eleven...
Source: Familial Cancer - May 19, 2020 Category: Cancer & Oncology Source Type: research

Biallelic NF1 inactivation in high grade serous ovarian cancers from patients with neurofibromatosis type 1
AbstractNeurofibromatosis type 1 (NF1) is a multisystem disorder caused by germline heterozygousNF1 loss-of-function variants. TheNF1 gene encodes neurofibromin, a RAS GTPase-activating protein, which functions by down-regulating RAS/RAF/MAPK-signalling pathways. SomaticNF1 aberrations frequently occur in sporadic ovarian cancer (OC), but the incidence of OC in NF1 patients is rare. Here we report the germline and somatic findings for two unrelated patients with NF1 and high-grade serous OC. Germline testing revealed a heterozygousNF1 pathogenic variant in each patient, c.7096_7101del (p.Asn2366_Phe2367del) and c.964delA (...
Source: Familial Cancer - May 12, 2020 Category: Cancer & Oncology Source Type: research

Evaluation of implementation of risk management guidelines for carriers of pathogenic variants in mismatch repair genes: a nationwide audit of familial cancer clinics
ConclusionThese results indicate that there is scope to further increase provision of advice at FCCs to ensure that all carriers receive recommendations about evidence-based risk management. A multi-pronged behaviour change and implementation science approach tailored to specific barriers is likely to be needed to achieve optimal clinician behaviours and outcomes for carriers. (Source: Familial Cancer)
Source: Familial Cancer - May 8, 2020 Category: Cancer & Oncology Source Type: research

MLH1 intronic variants mapping to  + 5 position of splice donor sites lead to deleterious effects on RNA splicing
AbstractGermline pathogenic variants in the DNA mismatch repair genes (MMR):MLH1,MSH2,MSH6, andPMS2, are causative of Lynch syndrome (LS). However, many of the variants mapping outside the invariant splice site positions (IVS  ± 1, IVS ± 2) are classified as variants of unknown significance (VUS). Three such variants (MLH1 c.588+5G>C, c.588+5G>T and c.677+5G>A) were identified in 8 unrelated LS families from Argentina, Brazil and Chile. Herein, we collected clinical information on these families and performed segregation analysis and RNA splicing studies to assess the impl...
Source: Familial Cancer - May 3, 2020 Category: Cancer & Oncology Source Type: research

Characterization of a germline splice site variant MLH1 c.678-3T & gt;A in a Lynch syndrome family
In this report, we describe a 42-year-old female with Lynch syndrome who carries a germline variant,MLH1 c.678-3T>A, in the splice acceptor site of intron 8. Functional studies and semiquantitative analysis demonstrated that this variant causes a significant increase in the transcripts with exon 9 or exon 9 and 10 deletions, which presumably leads to premature protein truncation or abnormal protein. In addition, we also observed MSI-H and loss of MLH1 by IHC in patient ’s tumor tissue. This variant also segregated with Lynch Syndrome related cancers in three affected family members. Based on these evidence, theMLH...
Source: Familial Cancer - April 29, 2020 Category: Cancer & Oncology Source Type: research

Cumulative risk of skin cancer in patients with Li-Fraumeni syndrome
AbstractLi-Fraumeni syndrome (LFS) is an inherited cancer syndrome, characterized by an early onset of various types of cancers. LFS is associated with a germline mutation in theTP53 gene. The risk of developing skin cancer in patients with LFS is unknown. To evaluate the cumulative risk of skin cancer in patients with LFS and to compare this risk to the general Dutch population. In this retrospective cohort study, all provenTP53 mutation carriers in the Netherlands Cancer Institute were included from their first visit to the Institute until June 2017. Medical charts and pathology reviews cross-referenced with PALGA, the n...
Source: Familial Cancer - April 29, 2020 Category: Cancer & Oncology Source Type: research

Primary fallopian tube carcinoma (PFTC) in a BRIP-1 mutation carrier: the first case report
AbstractSome hereditary ovarian cancer cases can be associated with a mutation of a gene involved in the DNA double-strand break repair system other than BRCA, such as BRIP1. This mutation is an emerging indication for prophylactic risk-reducing salpingo-oophorectomy (RRSO): however, anomalous tubal pathologic lesions have not yet been reported during RRSO performed for this specific indication (BRIP1), as largely reported for BRCA mutation carriers. An asymptomatic 64-year-old woman with a family history of ovarian and breast cancer agreed to undergo RRSO for a pathogenic variant of the BRIP1 gene (heterozygous NM_03204...
Source: Familial Cancer - April 23, 2020 Category: Cancer & Oncology Source Type: research

Systematic development of a training program for healthcare professionals to improve communication about breast cancer genetic counseling with low health literate patients
AbstractThere is a disproportionate underuse of genetic testing in breast cancer patients from lower education or migrant background. Within these groups, communication about referral to genetic counseling appears challenging due to limited health literacy and cultural barriers. Our aim was to develop and evaluate a training program for healthcare professionals (breast surgeons and specialized nurses), to increase effective communication. We systematically developed a blended training program based on patients ’ and healthcare professionals’ needs and preferences. Prior to the training, we assessed awareness, k...
Source: Familial Cancer - April 21, 2020 Category: Cancer & Oncology Source Type: research

Highly aggressive thoracic desmoid tumors in adolescent siblings with fatal outcomes in an FAP kindred: a need for increased vigilance and intervention in at-risk AYAs
AbstractDesmoid tumors are a manifestation of familial adenomatous polyposis (FAP), associated with mutation of theAPC gene. Although considered benign tumors, desmoids can be aggressive and cause considerable morbidity. Known risk factors for desmoid tumor growth include location of mutations within theAPC gene, family history of desmoid tumors, previous surgery, female gender, and pregnancy. Desmoids occur at diverse sites, commonly within the abdomen or at sites of previous surgery; thoracic desmoids are relatively uncommon. Reported here is a highly desmoid tumor-prone FAP family with a truncating mutation in theAPC ge...
Source: Familial Cancer - April 12, 2020 Category: Cancer & Oncology Source Type: research

Waiting and “weighted down”: the challenge of anticipatory loss for individuals and families with Li-Fraumeni Syndrome
In this study, losses were compounded by profound uncertainty, a chronic feature of LFS, which compromised mourning. Long-term engagement of menta l health providers with bereavement training, in partnership with genetics providers, can provide invaluable educational and psychological support to families as they navigate these implacable challenges. (Source: Familial Cancer)
Source: Familial Cancer - March 27, 2020 Category: Cancer & Oncology Source Type: research

Genetic health professionals ’ experiences with initiating reanalysis of genomic sequence data
AbstractDespite the increased diagnostic yield associated with genomic sequencing (GS), a sizable proportion of patients do not receive a genetic diagnosis at the time of the initial GS analysis. Systematic data reanalysis leads to considerable increases in genetic diagnosis rates yet is time intensive and leads to questions of feasibility. Few policies address whether laboratories have a duty to reanalyse and it is unclear how this impacts clinical practice. To address this, we interviewed 31 genetic health professionals (GHPs) across Europe, Australia and Canada about their experiences with data reanalysis and variant re...
Source: Familial Cancer - March 20, 2020 Category: Cancer & Oncology Source Type: research

Analysis of 3297 individuals suggests that the pathogenic germline 5 ′-UTR variant BRCA1 c.-107A  & gt;  T is not common in south-east Germany
In this study we aim to determine the prevalence of the recently identified pathogenicBRCA1 variant c.-107A  >  T in the south-east German population. This variant causes the epigenetic silencing of theBRCA1 promotor and has been detected in two independent families from the UK without a germlineBRCA1 orBRCA2 pathogenic variant. A total of 3297 individuals with suspicion of hereditary breast and ovarian cancer and fulfilling the clinical criteria necessary for genetic testing in Germany were analyzed for presence of the variant by a Kompetitive Allele-Specific PCR (KASP) assay or direct Sanger sequencing. ...
Source: Familial Cancer - March 20, 2020 Category: Cancer & Oncology Source Type: research

De novo SDHB gene mutation in a family with extra-adrenal paraganglioma
We present the second case of a family with ade novo SDHB mutation. (Source: Familial Cancer)
Source: Familial Cancer - March 20, 2020 Category: Cancer & Oncology Source Type: research

Patient-reported burden of intensified surveillance and surgery in high-risk individuals under pancreatic cancer surveillance
In conclusion, in individuals at high risk for pancreatic cancer, intensified surveillance temporarily increased cancer worries, without affecting general anxiety or depression. Although pancreatic surgery led to substa ntial co-morbidity, quality of life was similar to the general population, and surgery did not negatively affect the attitude towards surveillance. (Source: Familial Cancer)
Source: Familial Cancer - March 18, 2020 Category: Cancer & Oncology Source Type: research

Lack of evidence for CDK12 as an ovarian cancer predisposing gene
AbstractCDK12 variants were investigated as a genetic susceptibility to ovarian cancer in a series of 416 unrelated and consecutive patients with ovarian carcinoma and who carry neither germlineBRCA1 norBRCA2 pathogenic variant. The presence ofCDK12 variants was searched in germline DNA by massive parallel sequencing on pooled DNAs. The lack of detection of deleterious variants and the observed proportion of missense variants in the series of ovarian carcinoma patients as compared with all human populations strongly suggests thatCDK12 is not an ovarian cancer predisposing gene. (Source: Familial Cancer)
Source: Familial Cancer - March 13, 2020 Category: Cancer & Oncology Source Type: research

Collaborative Group of the Americas on Inherited Gastrointestinal Cancer Position statement on multigene panel testing for patients with colorectal cancer and/or polyposis
AbstractMultigene panel tests for hereditary cancer syndromes are increasingly utilized in the care of colorectal cancer (CRC) and polyposis patients. However, widespread availability of panels raises a number of questions including which patients should undergo testing, which genes should be included on panels, and the settings in which panels should be ordered and interpreted. To address this knowledge gap, key questions regarding the major issues encountered in clinical evaluation of hereditary CRC and polyposis were designed by the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer Position Statem...
Source: Familial Cancer - March 13, 2020 Category: Cancer & Oncology Source Type: research

Do the risks of Lynch syndrome-related cancers depend on the parent of origin of the mutation?
AbstractIndividuals who carry pathogenic mutations in DNA mismatch repair (MMR) genes have high risks of cancer, and small studies have suggested that these risks depend on the sex of the parent from whom the mutation was inherited. We have conducted the first large study of such a parent-of-origin effect (POE). Our study was based on all MMR gene mutation carriers and their relatives in the Colon Cancer Family Registry, comprising 18,226 people. The POE was estimated as a hazard ratio (HR) using a segregation analysis approach that adjusted for ascertainment. HR  = 1 corresponds to no POE and HR > ...
Source: Familial Cancer - February 26, 2020 Category: Cancer & Oncology Source Type: research

Perceptions of risk and reward in BRCA1 and BRCA2 mutation carriers choosing salpingectomy for ovarian cancer prevention
In conclusion, mostBRCA mutation carriers undergoing risk-reducing salpingectomy are satisfied with their decision and have lower risk perception after salpingectomy, though some older mutation carriers did not plan on future oophorectomy. Salpingectomy with delayed oophorectomy inBRCA mutation carriers remains investigational and should preferably be performed within a clinical trial to prevent introduction of an innovation before safety has been proven. (Source: Familial Cancer)
Source: Familial Cancer - February 23, 2020 Category: Cancer & Oncology Source Type: research