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 1.5–11),p = 0.009 for pooled control gro...
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 women r...
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 implication of these VUS in LS etiol...
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, theMLH1 c....
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_0320...
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, knowledge...
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. Since we d...
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
