Male Breast Cancer: Results of the Application of Multigene Panel Testing to an Italian Cohort of Patients

Overview

Journal Diagnostics (Basel)

Specialty Radiology

Date 2020 May 6

PMID 32365798

Citations 9

Authors

Gianluca Tedaldi

Michela Tebaldi

Valentina Zampiga

Ilaria Cangini

Francesca Pirini

Elisa Ferracci

Rita Danesi

Valentina Arcangeli

Mila Ravegnani

Giovanni Martinelli

Fabio Falcini

Paola Ulivi

Daniele Calistri

Affiliations

Soon will be listed here.

Abstract

Male breast cancer (MBC) is a rare tumor, accounting for less than 1% of all breast cancers. In MBC, genetic predisposition plays an important role; however, only a few studies have investigated in depth the role of genes other than and . We performed a Next-Generation Sequencing (NGS) analysis with a panel of 94 cancer predisposition genes on germline DNA from an Italian case series of 70 patients with MBC. Moreover, we searched for large deletions/duplications of genes through the Multiplex Ligation-dependent Probe Amplification (MLPA) technique. Through the combination of NGS and MLPA, we identified three pathogenic variants in the gene and six in the gene. Besides these alterations, we found six additional pathogenic/likely-pathogenic variants in , , , , and genes. From our study, and emerge as the main genes associated with MBC risk, but also other genes seem to be associated with the disease. Indeed, some of these genes have already been implicated in female breast cancer predisposition, but others are known to be involved in other types of cancer. Consequently, our results suggest that novel genes could be involved in MBC susceptibility, shedding new light on their role in cancer development.

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References

Tedaldi G, Pirini F, Tebaldi M, Zampiga V, Cangini I, Danesi R . Multigene Panel Testing Increases the Number of Loci Associated with Gastric Cancer Predisposition. Cancers (Basel). 2019; 11(9). PMC: 6769562. DOI: 10.3390/cancers11091340. View

Bell D, Gore I, Okimoto R, Godin-Heymann N, Sordella R, Mulloy R . Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Genet. 2005; 37(12):1315-6. DOI: 10.1038/ng1671. View

Testa J, Cheung M, Pei J, Below J, Tan Y, Sementino E . Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet. 2011; 43(10):1022-5. PMC: 3184199. DOI: 10.1038/ng.912. View

Silvestri V, Rizzolo P, Falchetti M, Zanna I, Masala G, Palli D . Mutation screening of RAD51C in male breast cancer patients. Breast Cancer Res. 2011; 13(1):404. PMC: 3109583. DOI: 10.1186/bcr2823. View

Silvestri V, Rizzolo P, Zanna I, Falchetti M, Masala G, Bianchi S . PALB2 mutations in male breast cancer: a population-based study in Central Italy. Breast Cancer Res Treat. 2010; 122(1):299-301. DOI: 10.1007/s10549-010-0797-z. View

Campbell P, Morton P, Takeichi T, Salam A, Roberts N, Proudfoot L . Epithelial inflammation resulting from an inherited loss-of-function mutation in EGFR. J Invest Dermatol. 2014; 134(10):2570-2578. PMC: 4090136. DOI: 10.1038/jid.2014.164. View

Pilarski R, Cebulla C, Massengill J, Rai K, Rich T, Strong L . Expanding the clinical phenotype of hereditary BAP1 cancer predisposition syndrome, reporting three new cases. Genes Chromosomes Cancer. 2013; 53(2):177-82. PMC: 4041196. DOI: 10.1002/gcc.22129. View

Ohtsuka K, Ohnishi H, Fujiwara M, Morii T, Matsushima S, Ogura W . Predisposition to Lung Adenocarcinoma in a Family Harboring the Germline V843I Mutation. JCO Precis Oncol. 2020; 3. PMC: 7446308. DOI: 10.1200/PO.19.00104. View

Swensen J, Hoffman M, Skolnick M, Neuhausen S . Identification of a 14 kb deletion involving the promoter region of BRCA1 in a breast cancer family. Hum Mol Genet. 1997; 6(9):1513-7. DOI: 10.1093/hmg/6.9.1513. View

10.

Li H, Durbin R . Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009; 25(14):1754-60. PMC: 2705234. DOI: 10.1093/bioinformatics/btp324. View

11.

Iqbal J, Ragone A, Lubinski J, Lynch H, Moller P, Ghadirian P . The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer. 2012; 107(12):2005-9. PMC: 3516682. DOI: 10.1038/bjc.2012.483. View

12.

Ding Y, Steele L, Kuan C, Greilac S, Neuhausen S . Mutations in BRCA2 and PALB2 in male breast cancer cases from the United States. Breast Cancer Res Treat. 2010; 126(3):771-8. PMC: 3059396. DOI: 10.1007/s10549-010-1195-2. View

13.

Rizzolo P, Silvestri V, Tommasi S, Pinto R, Danza K, Falchetti M . Male breast cancer: genetics, epigenetics, and ethical aspects. Ann Oncol. 2013; 24 Suppl 8:viii75-viii82. DOI: 10.1093/annonc/mdt316. View

14.

Tai Y, Domchek S, Parmigiani G, Chen S . Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007; 99(23):1811-4. PMC: 2267289. DOI: 10.1093/jnci/djm203. View

15.

Cybulski C, Gorski B, Huzarski T, Masojc B, Mierzejewski M, Debniak T . CHEK2 is a multiorgan cancer susceptibility gene. Am J Hum Genet. 2004; 75(6):1131-5. PMC: 1182149. DOI: 10.1086/426403. View

16.

Akbari M, Tonin P, Foulkes W, Ghadirian P, Tischkowitz M, Narod S . RAD51C germline mutations in breast and ovarian cancer patients. Breast Cancer Res. 2010; 12(4):404. PMC: 2949649. DOI: 10.1186/bcr2619. View

17.

Apostolou P, Fostira F . Hereditary breast cancer: the era of new susceptibility genes. Biomed Res Int. 2013; 2013:747318. PMC: 3618918. DOI: 10.1155/2013/747318. View

18.

van der Leest C, Wagner A, Pedrosa R, Aerts J, Dinjens W, Dubbink H . Novel V834L Germline Mutation Associated With Familial Lung Adenocarcinoma. JCO Precis Oncol. 2020; 2. PMC: 7446426. DOI: 10.1200/PO.17.00266. View

19.

Walsh T, Casadei S, Coats K, Swisher E, Stray S, Higgins J . Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA. 2006; 295(12):1379-88. DOI: 10.1001/jama.295.12.1379. View

20.

Fackenthal J, Marsh D, Richardson A, Cummings S, Eng C, Robinson B . Male breast cancer in Cowden syndrome patients with germline PTEN mutations. J Med Genet. 2001; 38(3):159-64. PMC: 1734834. DOI: 10.1136/jmg.38.3.159. View