title: Copy number alterations of the H2AFX gene in sporadic breast cancer patients.
abstract: In addition to being a structural component of chromatin, histone H2AX also has an important role in preserving genetic integrity. The histone H2AFX gene maps to the chromosome region 11q23.2 approximately 11q23.3 that is deleted in most human cancers. Mouse model studies also have clearly shown its involvement in tumorigenesis in a dosage-dependent manner. Therefore, in this study, DNA from 65 paired sporadic breast cancer tissues was systematically screened for gene mutations and changes in gene copy numbers. Although whole H2AFX gene scans showed an absence of mutation in the studied samples, the H2AFX gene copy number was altered in 37% of tumor samples. Furthermore, a twofold reduction in gene copy number in the MCF7 cell line strongly suggests the involvement of H2AFX alteration in breast carcinogenesis. Analysis of clinicopathologic association revealed a convincing correlation with positive estrogen/progesterone receptor status. To our knowledge, this is the first report of a change in H2AFX gene copy number in human cancer.
authors.affiliation: National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University (JNU), Aruna Asafali Marg, New Delhi-110067, India.
authors.forename: Niloo
authors.initials: N
authors.lastname: Srivastava
authors.forename: Sailesh
authors.initials: S
authors.lastname: Gochhait
authors.forename: Pawan
authors.initials: P
authors.lastname: Gupta
authors.forename: Rameshwar N K
authors.initials: RN
authors.lastname: Bamezai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics*; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage; D005820:Genetic Testing; D006367:HeLa Cells; D006657:Histones / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D014407:Tumor Cells, Cultured
chemical_list: C468783:H2AX protein, human; D006657:Histones