Increased copy number at 20q13 in breast cancer: defining the critical region and exclusion of candidate genes.

Studies by comparative genomic hybridization have indicated that a major new locus for DNA amplification in breast cancer is 20q13 and suggested that this genetic event is associated with aggressive clinical behavior. We used interphase fluorescence in situ hybridization with anonymous cosmid probes and gene-specific P1 clones to determine the minimal common region of increased copy number and to study involvement of known genes at 20q13. Based on high-level copy number increases (3 to 10-fold) found with one or more probes in 5 of 14 (35%) breast cancer cell lines and in 3 of 36 (8%) primary tumors, the critical region was narrowed to approximately 1.5 megabases at 20q13.2 defined by fractional length pter values 0.81-0.84. Previously known genes were excluded as candidates, implying that this chromosomal region harbors a novel oncogene that contributes to the malignant progression of breast cancer.

[1]  W. Kuo,et al.  A physical map of chromosome 20 established using fluorescence in situ hybridization and digital image analysis. , 1995, Genomics.

[2]  T. Visakorpi,et al.  Improved technique for analysis of formalin-fixed, paraffin-embedded tumors by fluorescence in situ hybridization. , 1994, Cytometry.

[3]  J Piper,et al.  Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. Vijver,et al.  Molecular genetic changes in human breast cancer. , 1993 .

[5]  G van den Engh,et al.  Estimating genomic distance from DNA sequence location in cell nuclei by a random walk model. , 1992, Science.

[6]  D. Pinkel,et al.  ERBB2 amplification in breast cancer analyzed by fluorescence in situ hybridization. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Foekens,et al.  Sporadic amplification of the insulin-like growth factor 1 receptor gene in human breast tumors. , 1992, Cancer research.

[8]  D. Birnbaum,et al.  BEK and FLG, two receptors to members of the FGF family, are amplified in subsets of human breast cancers. , 1991, Oncogene.

[9]  G Hermanson,et al.  High-resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. , 1990, Science.

[10]  M. Schwab,et al.  Amplification of cellular oncogenes: A predictor of clinical outcome in human cancer , 1990, Genes, Chromosomes and Cancer.

[11]  M. Skolnick,et al.  Report of the committee on the genetic constitution of chromosome 20. , 1990, Cytogenetics and cell genetics.

[12]  G. Wahl,et al.  Recent progress in understanding mechanisms of mammalian DNA amplification , 1989, Cell.

[13]  M. Schwab,et al.  Oncogene amplification in tumor cells. , 1986, Advances in cancer research.