Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jan;99(1):166-175.
doi: 10.1111/cge.13864. Epub 2020 Oct 21.

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

Mathias Cavaillé  1   2 , Nancy Uhrhammer  1   2 , Maud Privat  1   2 , Flora Ponelle-Chachuat  1   2 , Mathilde Gay-Bellile  1   2 , Mathis Lepage  1 , Sandrine Viala  1   2 , Yannick Bidet  1   2 , Yves-Jean Bignon  1   2
Affiliations

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

Mathias Cavaillé et al. Clin Genet. 2021 Jan.

Abstract

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.

Keywords: HBOC; HNPCC; double mutation; incidental findings ATM; panel sequencing; predisposition to cancer.

PubMed Disclaimer

Conflict of interest statement

The authors declare non conflict of interest. The study has been approved by personal protection committee (IRB: 2020 / CE57)

Figures

FIGURE 1
FIGURE 1
Indications of analysis, panel performed and detection rates. The detection rate is significantly higher in HBOC indication (P<.001), and higher in digestive indications. HBOC: Hereditary Breast and Ovarian Cancer, HNPCC: Hereditary Non Polyposis Colorectal Cancer, FAP / AFAP: Familial adenomatous polyposis / Attenuated Familial Adenomatous Polyposis, GIST: Gastro‐Intestinal Stromal Tumor, MEN1: Multiple endocrine neoplasia type 1, MEN2: Multiple endocrine neoplasia type 2, PHEO – PGL: Pheochromocytoma – Paraganglioma, PA: Pituitary Adenoma, BHD: Birt‐Hogg‐Dubé, VHL: Von Hippel Lindau, NF1: Neurobromatosis Type 1, NF2: Neurobromatosis Type 2
FIGURE 2
FIGURE 2
Genes with a pathogenic or probably pathogenic mutation identified in HBOC cases. Class 4 and 5 variants were identified using EP (blue) and OP (red) according to clinical presentation. ATM and BRIP1 have been associated significantly to HBOC patients in comparison to general population. Incidental findings include high penetrance genes CDKN2A, BAP1, NF1, MSH6, PMS2, RET and TMEM127. The heterozygous variants in MUTYH are not presented [Colour figure can be viewed at wileyonlinelibrary.com]
FIGURE 3
FIGURE 3
Genes with a pathogenic or probably pathogenic mutation identified in digestive cases. Class 4 and 5 variants were identified using EP (blue) and OP (red) according to clinical presentation. BRCA2 represents the third most frequently mutated gene. It is significantly associated to digestive indication. Others incidental findings included ATM, PALB2, NBN, NF1, and SDHA [Colour figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Kamps R et al. Next‐generation sequencing in oncology: genetic diagnosis, risk prediction and cancer classification. Int J Mol Sci. 2017;18(2):308. - PMC - PubMed
    1. Nielsen FC, van Overeem Hansen T, Sørensen CS. Hereditary breast and ovarian cancer: new genes in confined pathways. Nat. Rev Cancer. 2016;16:599‐612. - PubMed
    1. Valle L. Recent discoveries in the genetics of familial colorectal cancer and polyposis. Clin. Gastroenterol. Hepatol. 2017;15:809‐819. - PubMed
    1. Sokolenko AP et al. Identification of novel hereditary cancer genes by whole exome sequencing. Cancer Lett. 2015;369:274‐288. - PubMed
    1. Richards S et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med. 2015;17:405‐424. - PMC - PubMed

MeSH terms

Substances