J Breast Cancer.  2017 Mar;20(1):104-107. 10.4048/jbc.2017.20.1.104.

BRIP1/FANCJ Mutation Analysis in a Family with History of Male and Female Breast Cancer in India

• Venkateshwari A
• Clark DW
• Nallari P
• Vinod C
• Kumarasamy T
• Reddy G
• Jyothy A
• Kumar MV
• Ramaiyer R
• Palle K

• KMID: 2379405
• DOI: http://doi.org/10.4048/jbc.2017.20.1.104

Abstract

Male breast cancer (MBC) is a rare and poorly studied disease that is a growing global health problem. Interestingly, both the molecular basis of MBC and its histological profile are often quite distinct from the far more prevalent female breast cancer, emphasizing the need for increased focus on MBC. Here, we present a case report of an MBC patient from India with a strong familial history of breast cancer. This patient was normal for BRCA1/2 and many other common breast cancer-associated genes. However, upon further analysis, the individual was found to possess two mutations in the DNA helicase and tumor suppressor gene BRIP1, including a silent mutation at residue 879 as well as a P919S variant. Other family members were also screened for these mutations. To the best of our knowledge, this is the first report of BRIP1 mutation in MBC in the Indian population.

Keyword

BACH1 protein; Breast neoplasms; Mutation; Tumor suppressor gene

MeSH Terms

Breast Neoplasms*
Breast Neoplasms, Male
Breast*
DNA
Female*
Genes, Tumor Suppressor
Global Health
Humans
India*
Male*
Silent Mutation
DNA

Figure

• 

  Figure 1 Pedigree showing the familial history of breast cancer. The disease history of the male breast cancer patient discussed in this study, denoted as Proband (arrow), showing the mother, sister, and daughter, who all died of breast cancer. The chromatograms show that the patients as well as all four surviving descendants are heterozygous for the BRIP1 mutation P919S. The surviving individuals' current ages are presented below the pedigree box (the “yr” denotes years), and the ages in parentheses indicate the age of death. The “nd” below the boxes denotes that the ages were not disclosed or available.

• 

  Figure 2 Mutational map for the BRIP1 gene. (A) Depiction of the DNA sequence with nucleotide changes indicated. The exons are depicted by gray boxes and are to scale; however, introns are depicted as much smaller than actual size. The nucleotide substitutions yielding the E879E and P919S mutations are depicted by red lines and are located in exon 19. Exon 1 consists entirely of the 5′ untranslated region (UTR) sequence and exon 20 is largely the 3′ UTR sequence and has been truncated in this figure. (B) BRIP1 protein showing important structural features such as some previously identified breast cancer-associated mutations (black lines), as well as the BRCA1-binding domain and the S990 residue that is vital for the BRCA1 interaction. The mutations identified in this study are represented by the red lines.

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