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. 2021 May 7:11:649435.
doi: 10.3389/fonc.2021.649435. eCollection 2021.

Exome sequencing in BRCA1-2 candidate familias: the contribution of other cancer susceptibility genes

Gabriella Doddato  1   2 , Floriana Valentino  1   2 , Annarita Giliberti  1   2 , Filomena Tiziana Papa  1   2 , Rossella Tita  3 , Lucia Pia Bruno  1   2 , Sara Resciniti  1   2 , Chiara Fallerini  1   2 , Elisa Benetti  2 , Maria Palmieri  1   2 , Maria Antonietta Mencarelli  3 , Alessandra Fabbiani  1   2   3 , Mirella Bruttini  1   3 , Alfredo Orrico  4 , Margherita Baldassarri  1   2 , Francesca Fava  1   2   3 , Diego Lopergolo  1   2   3 , Caterina Lo Rizzo  3 , Vittoria Lamacchia  1   2   3 , Sara Mannucci  1   2   3 , Anna Maria Pinto  3 , Aurora Curr  1   2   3 , Virginia Mancini  5 ; Oncologic Multidisciplinary Team, Azienda Ospedaliera Universitaria Senese; Oncologic Multidisciplinary Team, Azienda Usl Toscana Sud Est; Francesca Mari  1   2   3 , Alessandra Renieri  1   2   3 , Francesca Ariani  1   2   3
Collaborators, Affiliations

Exome sequencing in BRCA1-2 candidate familias: the contribution of other cancer susceptibility genes

Gabriella Doddato et al. Front Oncol. .

Erratum in

  • Corrigendum: Exome Sequencing in BRCA1-2 Candidate Familias: The Contribution of Other Cancer Susceptibility Genes.
    Doddato G, Valentino F, Giliberti A, Papa FT, Tita R, Bruno LP, Resciniti S, Fallerini C, Benetti E, Palmieri M, Mencarelli MA, Fabbiani A, Bruttini M, Orrico A, Baldassarri M, Fava F, Lopergolo D, Rizzo CL, Lamacchia V, Mannucci S, Pinto AM, Currò A, Mancini V; Oncologic Multidisciplinary Team; Azienda Ospedaliera Universitaria Senese; Oncologic Multidisciplinary Team; Azienda Usl Toscana Sud Est; Mari F, Renieri A, Ariani F. Doddato G, et al. Front Oncol. 2021 Aug 17;11:740860. doi: 10.3389/fonc.2021.740860. eCollection 2021. Front Oncol. 2021. PMID: 34485163 Free PMC article.

Abstract

Hereditary Breast and Ovarian Cancer (HBOC) syndrome is a condition in which the risk of breast and ovarian cancer is higher than in the general population. The prevalent pathogenesis is attributable to inactivating variants of the BRCA1-2 highly penetrant genes, however, other cancer susceptibility genes may also be involved. By Exome Sequencing (WES) we analyzed a series of 200 individuals selected for genetic testing in BRCA1-2 genes according to the updated National Comprehensive Cancer Network (NCCN) guidelines. Analysis by MLPA was performed to detect large BRCA1-2 deletions/duplications. Focusing on BRCA1-2 genes, data analysis identified 11 cases with pathogenic variants (4 in BRCA1 and 7 in BRCA1-2) and 12 with uncertain variants (7 in BRCA1 and 5 in BRCA2). Only one case was found with a large BRCA1 deletion. Whole exome analysis allowed to characterize pathogenic variants in 21 additional genes: 10 genes more traditionally associated to breast and ovarian cancer (ATM, BRIP1, CDH1, PALB2, PTEN, RAD51C, and TP53) (5% diagnostic yield) and 11 in candidate cancer susceptibility genes (DPYD, ERBB3, ERCC2, MUTYH, NQO2, NTHL1, PARK2, RAD54L, and RNASEL). In conclusion, this study allowed a personalized risk assessment and clinical surveillance in an increased number of HBOC families and to broaden the spectrum of causative variants also to candidate non-canonical genes.

Keywords: BRCA1; BRCA2; cancer susceptibility genes; HBOC, ES (Excome Sequencing).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A–J) Pedigrees of patients carrying pathogenic variants in canonical genes. The gene and their variants are reported below the symbol of each proband. The arrows indicate the proband from each family. The black symbols indicate “HBOC-spectrum phenotypes” while striped symbols indicate “other neoplasms.” AC, abdominal cancer; BC, breast cancer; CC, colorectal cancer; GC, gastric cancer; GIC, gastrointestinal cancer; KC, kidney cancer; L, leukemia; LC, lung cancer; LvC, liver cancer; M, melanoma; OC, ovarian cancer; PC, pancreatic cancer; PrC, prostate cancer, S, sarcoma; SCC, spinal cord cancer; TC, tongue cancer; TyC, Thyroid cancer; UC, uterine cancer; X, not defined.
Figure 2
Figure 2
(A–L) Pedigrees of patients carrying pathogenic variants in non-canonical genes. The gene and their variants are reported below the symbol of each proband. The arrows indicate the proband from each family. The black symbols indicate “HBOC-spectrum phenotypes” while striped symbols indicate “other neoplasms.” Abbreviations as in Figure 1.
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