Hui-Yun Wang1, Danielle Greenawalt1, Xiangfeng Cui1, Irina V Tereshchenko1, Minjie Luo1, Qifeng Yang1, Marco A Azaro1, Guohong Hu1, Yi Chu1, James Y Li2, Li Shen1, Yong Lin3, Lianjun Zhang4, Honghua Li1
1Department of Molecular Genetics, Microbiology and Immunology/The Cancer Institute of New Jersey, Piscataway, New Jersey, 08854, USA
2Department of Computer Science, University of Maryland, Baltimore County, Baltimore, Maryland 21250, USA
3Department of Biometrics/The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854, USA
4Department of Forest and Natural Resources Management, College of Environment Science and Forestry, State University of New York, One Forestry Drive, Syracuse, New York, 13210, USA
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.
Keywords: Genetic alteration, single nucleotide polymorphism, genotyping, MCF-7 cell line, loss of heterozygosity, microarray