Identification of novel candidate genes by exome sequencing in Tunisian familial male breast cancer patients

Kridis, Wala Ben; Ayed-Guerfali, Dorra Ben; Ammous-Boukhris, Nihel; Ayadi, Wajdi; Kifagi, Chamseddine; Saguem, Ines; Sellami‐Boudawara, Tahya; Daoud, J.; Khanfir, Afef; Mokdad-Gargouri, Raja

doi:10.1007/s11033-020-05703-0

Cited by 6 publications

(4 citation statements)

References 42 publications

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“…In a cohort of Italian MBC (523 patients) analysed with a panel of 50 cancer-associated genes, PALB2 and RAD51D gene variants were significantly associated with MBC risk [ 21 ]. Whole exome sequencing performed on six MBC cases revealed germline variants in BRCA2, MSH5, DCC, ERBB3, NOTCH3, DIAPH1 and DNAH11 , but no statistical tests were performed in this study [ 17 ]. Our current study showed that our MBC cohort presents a distinct mutation profile when compared to a male noncancer NFE population by preferentially carrying at least one PV/LPV variant in the CDKN2A, HOXA9, NUTM2A, PALLD, PRCC, RECQL4, WRN, CYP1B1, BARD1, ERCC2, MRE11, MUTYH, RAD51C or XPC genes.…”

Section: Discussionmentioning

confidence: 99%

“…To date, the only clearly identified risk factor for MBC is the presence of a germline pathogenic or likely pathogenic variant (PV or LPV, respectively) in the BRCA2 or BRCA1 genes. Several studies have investigated the involvement of other genes in the risk of developing MBC, with populations ranging from 6 to 767 patients and panels ranging from 16 to 94 genes, predominantly restricted to genes previously implicated in FBC [ 13 , 14 , 15 , 16 ] or even at the exome scale (4600 genes), albeit only including 6 patients [ 17 ]. These studies have demonstrated the presence of PVs associated with the risk of MBC in the PALB2 (OR = 6.6–17.3), CHEK2 (OR = 3.7), ATM and RAD51D (OR = 8.6–10.2) genes (see review [ 18 ]).…”

Section: Introductionmentioning

confidence: 99%

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Multigene Panel Sequencing Identifies a Novel Germline Mutation Profile in Male Breast Cancer Patients

Al Saati,

Vande Perre,

Plenecassagnes

et al. 2023

IJMS

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Even though male breast cancer (MBC) risk encompasses both genetic and environmental aetiologies, the primary risk factor is a germline pathogenic variant (PV) or likely pathogenic variant (LPV) in BRCA2, BRCA1 and/or PALB2 genes. To identify new potential MBC-specific predisposition genes, we sequenced a panel of 585 carcinogenesis genes in an MBC cohort without BRCA1/BRCA2/PALB2 PV/LPV. We identified 14 genes carrying rare PVs/LPVs in the MBC population versus noncancer non-Finnish European men, predominantly coding for DNA repair and maintenance of genomic stability proteins. We identified for the first time PVs/LPVs in PRCC (pre-mRNA processing), HOXA9 (transcription regulation), RECQL4 and WRN (maintenance of genomic stability) as well as in genes involved in other cellular processes. To study the specificity of this MBC PV/LPV profile, we examined whether variants in the same genes could be detected in a female breast cancer (FBC) cohort without BRCA1/BRCA2/PALB2 PV/LPV. Only 5/109 women (4.6%) carried a PV/LPV versus 18/85 men (21.2%) on these genes. FBC did not carry any PV/LPV on 11 of these genes. Although 5.9% of the MBC cohort carried PVs/LPVs in PALLD and ERCC2, neither of these genes were altered in our FBC cohort. Our data suggest that in addition to BRCA1/BRCA2/PALB2, other genes involved in DNA repair/maintenance or genomic stability as well as cell adhesion may form a specific MBC PV/LPV signature.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multigene Panel Sequencing Identifies a Novel Germline Mutation Profile in Male Breast Cancer Patients

Al Saati,

Vande Perre,

Plenecassagnes

et al. 2023

IJMS

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“…These reports have revealed a total of only 18 distinct mutations of which 12 are localized within BRCA1 gene including 2 large rearrangements encompassing exons 5 and 20. Among the identified mutations c.211dupA, c.5266dupC in BRCA1 and c.1310_1313delAAGA in BRCA2 were the most recurrent mutations encountered among the hereditary breast cancer cases (11,(15)(16)(17)(18)(19)(20)(21)(22)(23). Despite these efforts, the mutational spectrum of BRCA1/2 genes is still not well established.…”

Section: Introductionmentioning

confidence: 99%

Identification of Eleven Novel BRCA Mutations in Tunisia: Impact on the Clinical Management of BRCA Related Cancers

et al. 2021

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BackgroundBreast cancer is the world’s most common cancer among women. It is becoming an increasingly urgent problem in low- and middle-income countries (LMICs) where a large fraction of women is diagnosed with advanced-stage disease and have no access to treatment or basic palliative care. About 5-10% of all breast cancers can be attributed to hereditary genetic components and up to 25% of familial cases are due to mutations in BRCA1/2 genes. Since their discovery in 1994 and 1995, as few as 18 mutations have been identified in BRCA genes in the Tunisian population. The aim of this study is to identify additional BRCA mutations, to estimate their contribution to the hereditary breast and ovarian cancers in Tunisia and to investigate the clinicopathological signatures associated with BRCA mutations.MethodsA total of 354 patients diagnosed with breast and ovarian cancers, including 5 male breast cancer cases, have been investigated for BRCA1/2 mutations using traditional and/or next generation sequencing technologies. Clinicopathological signatures associated with BRCA mutations have also been investigated.ResultsIn the current study, 16 distinct mutations were detected: 10 in BRCA1 and 6 in BRCA2, of which 11 are described for the first time in Tunisia including 3 variations that have not been reported previously in public databases namely BRCA1_c.915T>A; BRCA2_c.-227-?_7805+? and BRCA2_c.249delG. Early age at onset, family history of ovarian cancer and high tumor grade were significantly associated with BRCA status. BRCA1 carriers were more likely to be triple negative breast cancer compared to BRCA2 carriers. A relatively high frequency of contralateral breast cancer and ovarian cancer occurrence was observed among BRCA carriers and was more frequent in patients carrying BRCA1 mutations.ConclusionOur study provides new insights into breast and ovarian cancer genetic landscape in the under-represented North African populations. The prevalence assessment of novel and recurrent BRCA1/2 pathogenic mutations will enhance the use of personalized treatment and precise screening strategies by both affected and unaffected North African cancer cases.

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“…These reports have revealed a total of only 18 distinct mutations of which 12 are localized within BRCA1 gene including 2 large rearrangements encompassing exons 5 and 20. Among the identi ed mutations c.211dupA, c.5266dupC in BRCA1 and c.1310_1313delAAGA in BRCA2 were the most recurrent mutations encountered among the hereditary breast cancer cases [10,[14][15][16][17][18][19][20][21][22]. Despite these efforts, the mutational spectrum of BRCA1/2 genes is still not well established.…”

Section: Introductionmentioning

confidence: 99%

Identification of Eleven Novel BRCA Mutations in Tunisia: Impact on the Clinical Management of BRCA Related Cancers

Hamdi

Mighri

Boujemaa

et al. 2021

Preprint

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Background Breast cancer is the world's most common cancer among women. It is becoming an increasingly urgent problem in low- and middle-income countries (LMICs) where a large fraction of women is diagnosed with advanced-stage disease and have no access to treatment or basic palliative care. About 5-10% of all breast cancers can be attributed to hereditary genetic components and up to 25% of familial cases are due to mutations in BRCA1/2 genes. Since their discovery in 1994 and 1995, as few as 18 mutations have been identified in BRCA genes in the Tunisian population. The aim of this study is to identify additional BRCA mutations, to estimate their contribution to the hereditary breast and ovarian cancers in Tunisia and to investigate the clinicopathological signatures associated with BRCA mutations. Methods A total of 354 patients diagnosed with breast and ovarian cancers, including 5 male breast cancer cases, have been investigated for BRCA1/2 mutations using traditional and/or next generation sequencing technologies. Clinicopathological signatures associated with BRCA mutations have been also investigated. Results 16 distinct mutations were detected: 10 in BRCA1 and 6 in BRCA2, of which 11 are described for the first time in Tunisia including 3 variations that have not been reported previously in public databases namely BRCA1_c.915T>A; BRCA2_c.-227-?_7805+? and BRCA2_c.249delG. Early age at onset, family history of ovarian cancer and high tumor grade were significantly associated with BRCA status. BRCA1 carriers were more likely to be triple negative breast cancer compared to BRCA2 carriers. A relatively high frequency of contralateral breast cancer and ovarian cancer occurrence was observed among BRCA carriers and was more frequent in patients carrying BRCA1 mutations. Conclusion Our study provides new insights into breast and ovarian cancer genetic landscape in the under-represented North African populations. The prevalence assessment of novel and recurrent BRCA1/2 pathogenic mutations will enhance the use of personalized treatment and precise screening strategies by both affected and unaffected North African cancer cases.

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Identification of novel candidate genes by exome sequencing in Tunisian familial male breast cancer patients

Cited by 6 publications

References 42 publications

Multigene Panel Sequencing Identifies a Novel Germline Mutation Profile in Male Breast Cancer Patients

Multigene Panel Sequencing Identifies a Novel Germline Mutation Profile in Male Breast Cancer Patients

Identification of Eleven Novel BRCA Mutations in Tunisia: Impact on the Clinical Management of BRCA Related Cancers

Identification of Eleven Novel BRCA Mutations in Tunisia: Impact on the Clinical Management of BRCA Related Cancers

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