Ovarian carcinoma in children with constitutional mutation of SMARCA4: single-family report and literature review
In this study, we report genetic testing of a family with two children carrying pathogenic germline mutations ofSMARCA4 and summarize the course of SCCOHT in all pediatric patients reported in the literature with constitutional defects identified within theSMARCA4 locus. (Source: Familial Cancer)
Source: Familial Cancer - October 1, 2021 Category: Cancer & Oncology Source Type: research

Outcomes of retesting in patients with previously uninformative cancer genetics evaluations
This study adds to the limited body of literature on ret esting outcomes beyond first-lineBRCA analysis alone and confirms the utility of multigene panel testing. Retesting certain affected individuals when updated GT is available could result in earlier PV/LPV identification, significantly impacting screening recommendations and potentially reducing cancer-related morbidity and mortality. (Source: Familial Cancer)
Source: Familial Cancer - September 21, 2021 Category: Cancer & Oncology Source Type: research

Fibroadenoma in vulval ectopic breast tissue in a patient with PTEN  Hamartoma Tumour Syndrome
AbstractPTEN is a tumour suppressor gene involved in regulating cell division. Pathogenic germline variants inPTEN predispose to benign and malignant growths of numerous organs, including of the breast. In the following report, we describe the first documented case of a fibroadenoma developing in ectopic breast tissue of the vulva in a patient with a germline pathogenic variant inPTEN. This highlights the risk of hyperplasia developing in any breast tissue, including rare ectopic sites, particularly in patients with underlying germline variants in cancer susceptibility genes. (Source: Familial Cancer)
Source: Familial Cancer - September 15, 2021 Category: Cancer & Oncology Source Type: research

Eighth International Symposium on hereditary breast and ovarian cancer
(Source: Familial Cancer)
Source: Familial Cancer - September 15, 2021 Category: Cancer & Oncology Source Type: research

Uterine leiomyomatosis in adolescents and young adults (AYAs) may represent a narrow phenotypic variant of FH tumour predisposition syndrome
AbstractFH Tumour Predisposition Syndrome, also known as Hereditary Leiomyomatosis and renal cell cancer (HLRCC), or Reed Syndrome, is an autosomal dominant condition clinically characterized by multiple cutaneous leiomyomas, multiple early-onset uterine leiomyomas and early-onset renal cell cancer. Here we report a young female with FH Tumour Predisposition Syndrome with no clinical features except early-onset uterine leiomyomas. Whilst there is a significant history of uterine leiomyomas in her family, there is no history of cutaneous leiomyomas or renal cell cancer (RCC). Uterine leiomyomatosis i...
Source: Familial Cancer - September 14, 2021 Category: Cancer & Oncology Source Type: research

A de novo pathogenic variant in the MSH6 gene in a 52 years-old woman
AbstractLynch syndrome (LS) is a condition which predisposes individuals primarily to early-onset colorectal and endometrial cancer. LS is characterized by a germline pathogenic variant in one of the MMR (MisMatch Repair) gene, inducing a phenotype of microsatellite instability in the tumor, which may be associated with a loss of expression of MMR proteins detected by standard immunohistochemistry on tumor tissue. Most of the time, LS is inherited from a parent in whom the condition may not be known due to incomplete penetrance, but de novo pathogenic variant is a rare occurrence. Here, we describe the case of a 52-year-ol...
Source: Familial Cancer - September 14, 2021 Category: Cancer & Oncology Source Type: research

Unusual phenotypes in patients with a pathogenic germline variant in DICER1
AbstractPathogenic germlineDICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic missenseDICER1 variants in the RNase IIIb domain are linked to cause GLOW (global developmental delay, lung cysts, overgrowth, and Wilms ’ tumor) syndrome. Here, we report four families with germlineDICER1 pathogenic variants in which one member in each family had a more complex phenotype, including skeletal findings, facial dysmorphism and developmental abnormalities. The developmental features occur with a variable expressivity and incomplete penet...
Source: Familial Cancer - July 31, 2021 Category: Cancer & Oncology Source Type: research

Patient ethnicity and cascade genetic testing: a descriptive study of a publicly funded hereditary cancer program
This study provides further insight into uptake of cascade genetic testing by patient ethnicity. Examining patient ethnicity and cascade genetic testing rates helps to identify underserved populations. Our analysis highlights significant underrepresentation of North American Indigenous individuals for hereditary cancer cascade genetic testing, and helps recognize the need for development of culturally-safe alternatives to outreach and service promotion. (Source: Familial Cancer)
Source: Familial Cancer - July 7, 2021 Category: Cancer & Oncology Source Type: research

Novel MAPK/AKT-impairing germline NRAS variant identified in a melanoma-prone family
AbstractWhile several high-penetrance melanoma risk genes are known, variation in these genes fail to explain melanoma susceptibility in a large proportion of high-risk families. As part of a melanoma family sequencing study, including 435 families from Mediterranean populations we identified a novelNRAS variant (c.170A  >  C, p.D57A) in an Italian melanoma-prone family. This variant is absent in exomes in gnomAD, ESP, UKBiobank, and the 1000 Genomes Project, as well as in 11,273 Mediterranean individuals and 109 melanoma-prone families from the US and Australia. This variant occurs in the GTP-binding pocket of NRAS...
Source: Familial Cancer - July 3, 2021 Category: Cancer & Oncology Source Type: research

Surveillance recommendations for DICER1 pathogenic variant carriers: a report from the SIOPE Host Genome Working Group and CanGene-CanVar Clinical Guideline Working Group
AbstractDICER1 syndrome is a rare genetic disorder that predisposes to a wide spectrum of tumors. Developing surveillance protocols for this syndrome is challenging because uncertainty exists about the clinical efficacy of surveillance, and appraisal of potential benefits and harms vary. In addition, there is increasing evidence that germlineDICER1 pathogenic variants are associated with lower penetrance for cancer than previously assumed. To address these issues and to harmonize DICER1 syndrome surveillance programs within Europe, the Host Genome Working Group of the European branch of the International Society of Pediatr...
Source: Familial Cancer - June 25, 2021 Category: Cancer & Oncology Source Type: research

PTCH2 is not a strong candidate gene for gorlin syndrome predisposition
AbstractA number of case/family reports have proposedPTCH2 as a putative Gorlin Syndrome (GS) gene, but evidence to support this is lacking. We assessed our cohort of 21PTCH1/SUFU negative GS families forPTCH2 variants and assessed current evidence from reported cases/families and population data. In ourPTCH1/SUFU variant negative GS cohort (25% of total), no pathogenic or likely pathogenicPTCH2 variants were identified. In addition, none of the previously publishedPTCH2 variants in GS families/cases could be considered pathogenic or likely pathogenic using current guidelines. The absence of clear pathogenic variants in GS...
Source: Familial Cancer - June 25, 2021 Category: Cancer & Oncology Source Type: research

A patient with very early onset FH-deficient renal cell carcinoma diagnosed at age seven
This report describes a seven-year-old (84-month-old) male who developed a large right kidney tumor with multiple cystic lesions that contained enhanced solid components. There was no evidence of distant metastasis. The male patient underwent right nephrectomy and has been recovering w ell without metastasis or recurrence. Pathological examination revealed that tumor cells with relatively prominent nucleoli and surrounded by halos, were located in a limited area. Immunohistochemical staining was negative for FH. Whole-exome sequencing identified his germline variant in theFH gene and its loss of heterozygosity in the tumor...
Source: Familial Cancer - June 22, 2021 Category: Cancer & Oncology Source Type: research

The paradigm of hematological malignant versus non-malignant manifestations, driven by primary immunodeficiencies: a complex interplay
AbstractHematological malignancies (HM) developed on underlying primary immunodeficiencies (PID) are rare and of unusual features. Differentiating between malignant and non-malignant lymphoproliferation in cases of pediatric hematology and oncology and revealing their molecular predisposition demonstrate the complex interplay between PID and HM. We retrospectively studied a case series of seven pediatric patients, all with PID with manifestations raising suspicion for HM or hypereosinophilic syndrome (HES) or confirmed HM of lymphoid origin. Combined immunodeficiency (CID) without detection of a known mutated gene or with ...
Source: Familial Cancer - June 15, 2021 Category: Cancer & Oncology Source Type: research

First international workshop of the ATM and cancer risk group (4-5 December 2019)
This report summarizes the meeting sessions content that covered the latest results in family-based and population-based studies, the importance of accurate variant classification, the effect of radiation exposures forATM variant carriers, and the characteristics of ATM-deficient tumors. The report concludes thatATM variant carriers outside of the context of Ataxia-Telangiectasia may benefit from effective cancer risk management and therapeutic strategies and that efforts to set up large-scale studies in the international framework to achieve this goal are necessary. (Source: Familial Cancer)
Source: Familial Cancer - June 14, 2021 Category: Cancer & Oncology Source Type: research

Utility of interim blood tests for cancer screening in Li-Fraumeni syndrome
AbstractComprehensive annual screening reduces cancer-related mortality in Li-Fraumeni syndrome (LFS), a cancer-prone disorder caused by pathogenic germlineTP53 variants. Blood tests at months 4 and 8 between annual screening are recommended but their effectiveness in early cancer detection has not been established. Interim blood counts and inflammatory biomarkers were evaluated in 132 individuals with LFS (112 adults, 87 female, median age 36  years [range 3–68], median follow-up 37 months [range 2–70]) and test abnormalities were observed in 225 (35%). Thirteen cancers in 12 individuals were diagnosed between annua...
Source: Familial Cancer - June 2, 2021 Category: Cancer & Oncology Source Type: research