Somatic mutations in the <i>BRCA2</i> gene and high frequency of allelic loss of <i>BRCA2</i> in sporadic male breast cancer

Kwiatkowska, Eliza; Teresiak, M.; Breborowicz, D; Maćkiewicz, Andrzej

doi:10.1002/ijc.10289

Cited by 18 publications

(14 citation statements)

References 16 publications

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“…It is also noteworthy that BRCA2 somatic mutations have also been reported in 21.8% of sporadic MBCs [22]. Furthermore, unlike in FBC, studies by Ottini et al .…”

Section: Discussionmentioning

confidence: 99%

PIK3CA mutations are frequently observed in BRCAX but not BRCA2-associated male breast cancer

Deb

Byrne

et al. 2013

Breast Cancer Res

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IntroductionAlthough a substantial proportion of male breast cancers (MBCs) are hereditary, the molecular pathways that are activated are unknown. We therefore examined the frequency and clinicopathological associations of the PIK3CA/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) pathways and their regulatory genes in familial MBC.MethodsHigh resolution melting analysis and confirmatory sequencing was used to determine the presence of somatic mutations in PIK3CA (exon 9 and 20), AKT1 (exon 4), KRAS (exon 2) and BRAF (exon 15) genes in 57 familial MBCs. Further analysis of the PIK3CA/mTOR pathway was performed using immunohistochemistry for the pAKT1, pS6 and p4EBP1 biomarkers.ResultsPIK3CA somatic mutations were identified in 10.5% (6 of 57) of cases; there were no AKT1, KRAS or BRAF somatic mutations. PIK3CA mutations were significantly more frequent in cancers from BRCAX patients (17.2%, 5/29) than BRCA2 (0%, 0/25) carriers (P = 0.030). Two BRCAX patients had an E547K mutation which has only been reported in one female breast cancer previously. PIK3CA mutation was significantly correlated with positive pS6 (83.3% vs. 32.0%, P = 0.024) and negative p4EBP1 (100% vs. 38.0%, P = 0.006) expression, but not pAKT expression. Expression of nuclear p4EBP1 correlated with BRCA2 mutation carrier status (68.0% vs. 38.7%, P = 0.035).ConclusionsSomatic PIK3CA mutation is present in familial male breast cancer but absent in BRCA2 carriers. The presence of two of the extremely rare E547K PIK3CA mutations in our cohort may have specific relevance in MBCs. Further study of PIK3CA in MBCs, and in particular BRCAX patients, may contribute to further establishing the relevance of specific PIK3CA mutations in MBC aetiology and in the identification of particular patient groups most likely to benefit from therapeutic targeting with the novel PIK3CA inhibitors that are currently in development.

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“…It is also noteworthy that BRCA2 somatic mutations have also been reported in 21.8% of sporadic MBCs [22]. Furthermore, unlike in FBC, studies by Ottini et al .…”

Section: Discussionmentioning

confidence: 99%

PIK3CA mutations are frequently observed in BRCAX but not BRCA2-associated male breast cancer

Deb

Byrne

et al. 2013

Breast Cancer Res

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“…Somatic mutations in breast cancer patients are also very rare in the second major susceptibility gene, BRCA2. One acquired frameshift mutation in BRCA2 was detected in 69 unselected samples of breast tumors (Weber et al, 1996) and the other in a series of 23 archival samples from male breast cancer patients (Kwiatkowska et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Novel somatic mutations in the BRCA1 gene in sporadic breast tumors

et al. 2005

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Germline mutations in two major susceptibility genes BRCA1 and BRCA2 contribute to the majority of inherited breast and ovarian cancers. Besides the germline mutation, tumor progression depends on the loss of a wild-type allele. Allelic losses in the BRCA1 and BRCA2 loci have also been detected in a high proportion of sporadic breast tumors, suggesting the role of these genes in the development of non-inherited breast cancer. Forty unselected breast tumors were analyzed for the loss of heterozygosity (LOH) at BRCA1 and BRCA2 regions and tumors with allelic deletions were screened for the presence of acquired genetic alterations in respective genes. 21.1% of 38 informative tumor samples carried LOH at the BRCA1 locus whereas 33.3% of 39 informative samples showed LOH at the BRCA2 locus. Pathogenic truncating mutations in the BRCA1 gene were found in two tumor samples with allelic losses, whereas no mutations were identified in the BRCA2 gene. Mutations were not detected in non-tumor samples from the same individuals, which indicated that the BRCA1 allele was inactivated by somatic mutations in tumor tissue. The c.1116G>A (1235G>A) nonsense mutation (p.W372X) belongs to the genetic abnormalities detected infrequently in hereditary tumors; the c.3862delG (3981delG) frameshift mutation (p.E1288fsX1306) is a novel gene alteration. The occurrence of inactivating somatic mutations in sporadic breast tumors suggested the role of the BRCA1 gene in tumorigenesis in at least a minor group of patients with non-familial breast cancer.

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“…In many tumours, loss of heterozygosity for the wild‐type allele of the BRCA2 and gene microsatellite instability was shown (Wingren et al. , 1997; Kwiatkowska et al. , 2002; Luqmani et al.…”

Section: Brca1/brca2mentioning

confidence: 99%

Review article Male breast cancer - an andrological disease: risk factors and diagnosis

Kŕause

2004

Andrologia

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Gynaecomastia, the enlargement of the male breast, is considered as an andrological disease. To date, a review on male breast cancer (MBC) has not been published in an andrological journal. The papers underlying this review were published from authors of different institutions: Clinical Genetics, Dermatology, Gynaecology, Internal Medicine, Oncology, Pathology, Psychiatry, Radiology and Surgery. MBC accounts for approximately 1% of breast cancer patients. A total of 182 men died of breast cancer in 1999, in Germany. In the US, 1500 new cases per year occur. MBC accounts for <5% of surgically removed breast lumps. Diseases with increased oestrogen action increase the risk of MBC. Mutations of distinct genes are estimated to account for up to roughly 10% of MBC. BRCA1 and BRCA2 gene mutations are responsible for approximately 80% of the families with hereditary breast cancer. The diagnosis of MBC is not possible without histological examination. Different diagnostic procedures such as clinical diagnosis, sonography, mammography, fine-needle biopsy and core needle facilitate the decision whether a biopsy is necessary.

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Somatic mutations in the BRCA2 gene and high frequency of allelic loss of BRCA2 in sporadic male breast cancer

Cited by 18 publications

References 16 publications

PIK3CA mutations are frequently observed in BRCAX but not BRCA2-associated male breast cancer

PIK3CA mutations are frequently observed in BRCAX but not BRCA2-associated male breast cancer

Novel somatic mutations in the BRCA1 gene in sporadic breast tumors

Review article Male breast cancer - an andrological disease: risk factors and diagnosis

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