Identification of BCL2L11 as a Candidate Gene for Hereditary Predisposition to Non-Medullary Thyroid Cancer Using Familial Whole-Exome-Sequencing.

Familial non-medullary thyroid cancer, defined as two or more affected first-degree relatives, accounts for 3%-9% of thyroid cancers. It is associated with more aggressive cancer, early age at diagnosis, multifocality, and increased risk of metastasis and recurrence. Although no high penetrance predisposing gene has been identified at present, the estimated contribution of genetics is significant.

Deciphering dual clinical entities associated with TP53 pathogenic variants: Insights from 53,085 HBOC panel analyses in French laboratories.

TP53 is included in most cancer predisposition multigene panels, especially those exploring Hereditary Breast and Ovarian Cancer (HBOC) predisposition. The purpose of this study was to define the contribution of TP53 pathogenic variants (PV) to the HBOC phenotype by collecting genotypes and phenotypes of 398 patients harboring a TP53 variant identified by 53,085 HBOC panel sequencing in 15 French laboratories. Heterozygous TP53 variants were identified in 0.

RNA Panel Sequencing Is an Effective Tool to Help Classify Splice Variants for Clinical Oncogenetic Diagnosis.

Routine gene panel analysis identifies pathogenic variants in clinically relevant genes. However, variants of unknown significance (VUSs) are commonly observed, many of which potentially have an impact on mRNA transcription and splicing. Several software programs attempt to predict the impact of variants on splicing and thus make it possible to select the variants for which it is important to study the effect on the transcripts.

Prevalence of Constitutional Pathogenic Variant in a Cohort of 348 Patients With Multiple Primary Cancer Addressed in Oncogenetic Consultation.

Introduction: Multiple primary malignancies (MPMs) refer to two or more primary malignant tumors in the same patient. MPMs are frequent: 18.4% of incident cancers represent a second or a higher primary cancer.

Identification of new candidate genes for the hereditary predisposition to uveal melanoma: IGCMU trial.

Introduction: Uveal melanoma (UM) is a rare ocular cancer. While germline mutations in genes such as BAP1 and MBD4 account for approximately 20% of familial UM cases, the hereditary factors underlying the remaining cases remain unknown. Epidemiological studies have suggested an increased risk of prostate cancer, thyroid cancer, and leukemia among patients with UM, indicating potential unidentified genetic predispositions.

Detection Rate and Spectrum of Pathogenic Variations in a Cohort of 83 Patients with Suspected Hereditary Risk of Kidney Cancer.

Hereditary predisposition to cancer affects about 3-5% of renal cancers. Testing criteria have been proposed in France for genetic testing of non-syndromic renal cancer. Our study explores the detection rates associated with our testing criteria.

Case Series of 11 Families (47 Carriers) Including Incidental Findings, Signet Ring Cell Colon Cancer and Review of the Literature.

Germline pathogenic variants in E-cadherin () confer high risk of developing lobular breast cancer and diffuse gastric cancer (DGC). The cumulative risk of DGC in carriers has been recently reassessed (from 40-83% by age 80 to 25-42%) and varies according to the presence and number of gastric cancers in the family. As there is no accurate estimate of the risk of gastric cancer in families without DGC, the International Gastric Cancer Linkage Consortium recommendation is not straightforward: prophylactic gastrectomy or endoscopic surveillance should be proposed for these families.

Diagnosis of PTEN mosaicism: the relevance of additional tumor DNA sequencing. A case report and review of the literature.

Background: PTEN hamartoma syndrome (PHTS) is an autosomal dominant disorder characterized by pathogenic variants in the tumor suppressor gene phosphatase and tensin homolog (PTEN). It is associated with an increased risk of muco-cutaneous features, hamartomatous tumors, and cancers. Mosaicism has been found in a few cases of patients with de novo PHTS, identified from blood samples.

Analysis of 11 candidate genes in 849 adult patients with suspected hereditary cancer predisposition.

Hereditary predisposition to cancer concerns between 5% and 10% of cancers. The main genes involved in the most frequent syndromes (hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome) were identified in the 1990s. Exploration of their functional pathways then identified novel genes for hereditary predisposition to cancer, and candidate genes whose involvement remains unclear.

Feedback of extended panel sequencing in 1530 patients referred for suspicion of hereditary predisposition to adult cancers.

High-throughput sequencing analysis represented both a medical diagnosis and technological revolution. Gene panel analysis is now routinely performed in the exploration of hereditary predisposition to cancer, which is becoming increasingly heterogeneous, both clinically and molecularly. We present 1530 patients with suspicion of hereditary predisposition to cancer, for which two types of analyses were performed: a) oriented according to the clinical presentation (n = 417), or b) extended to genes involved in hereditary predisposition to adult cancer (n = 1113).