Identification of possible genetic alterations in the breast cancer cell line MCF-7 using high-density SNP genotyping microarray

Abstract

Context:Cancer cell lines are used extensively in various research. Knowledge of genetic alterations in these lines is important for understanding mechanisms underlying their biology. However, since paired normal tissues are usually unavailable for comparison, precisely determining genetic alterations in cancer cell lines is difficult. To address this issue, a highly efficient and reliable method is developed. Aims: Establishing a highly efficient and reliable experimental system for genetic profiling of cell lines.Materials and Methods:A widely used breast cancer cell line, MCF-7, was genetically profiled with 4,396 single nucleotide polymorphisms (SNPs) spanning 11 whole chromosomes and two other small regions using a newly developed high-throughput multiplex genotyping approach.Results:The fractions of homozygous SNPs in MCF-7 (13.3%) were significantly lower than those in the control cell line and in 24 normal human individuals (25.1% and 27.4%, respectively). Homozygous SNPs in MCF-7 were found in clusters. The sizes of these clusters were significantly larger than the expected based on random allelic combination. Fourteen such regions were found on chromosomes 1p, 1q, 2q, 6q, 13, 15q, 16q, 17q and 18p in MCF-7 and two in the small regions.Conclusions:These results are generally concordant with those obtained using different approaches but are better in defining their chromosomal positions. The used approach provides a reliable way to detecting possible genetic alterations in cancer cell lines without paired normal tissues.

Plastics and carcinogenesis: The example of vinyl chloride

“…For example, molecular modeling of the BRCT1 domains of the normal and polymorphic forms of XRCC1 demonstrates that the 399 substitution produces significant conformational changes in this domain, including the loss of secondary structural features such as α-helices that can be critical for mediating protein-protein interactions that would allow XRCC1 to coordinate BER. [63] Also, studies of lymphoblasts from individuals of different genotypes exposed in vitro to the reactive metabolites of VC showed that cells with the XRCC1 399 homozygous variant Gln-Gln genotype had an approximate fourfold decrease in efficiency of repair of εA DNA adducts compared to cells with the homozygous wild-type Arg-Arg genotype [Table 2],[6064] resulting in an approximate 1.8-fold increase in mutation frequency in the polymorphic cells as measured by the HPRT assay.…”