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

• Published in: Clinical genetics Vol. 99; no. 1; pp. 166 - 175
• Main Authors: Cavaillé, Mathias, Uhrhammer, Nancy, Privat, Maud, Ponelle‐Chachuat, Flora, Gay‐Bellile, Mathilde, Lepage, Mathis, Viala, Sandrine, Bidet, Yannick, Bignon, Yves‐Jean
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-01-2021; Wiley
• Subjects: Breast cancer; Cancer; double mutation; Genes; HBOC; Heredity; HNPCC; incidental findings ATM; Life Sciences; Mutation; Original; Ovarian cancer; panel sequencing; Patients; predisposition to cancer; Sequence analysis; HNPCC; incidental findings ATM; double mutation; panel sequencing; predisposition to cancer; HBOC
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.13864

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). Extended panel analysis had a higher detection rate compared to oriented analysis in hereditary predisposition to breast / ovarian cancer (P < .001) and in digestive cancers (P < .094) (respectively 15% vs 5% and 19.3%, vs 12.5%). This higher detection is explained by the inclusion of moderate penetrance genes, as well as the identification of incident mutations and double mutations. Our study underscores the utility of proposing extended gene panel analysis to patients with suspicion of hereditary predisposition to adult cancer.