Candidate genes in breast cancer revealed by microarray-based comparative genomic hybridization of archived tissue.
Genomic imbalances in 31 formalin-fixed and paraffin-embedded primary tumors of advanced breast cancer were analyzed by microarray-based comparative genomic hybridization (matrix-CGH). A DNA chip was designed comprising 422 mapped genomic sequences including 47 proto-oncogenes, 15 tumor suppressor genes, as well as frequently imbalanced chromosomal regions. Analysis of the data was challenging due to the impaired quality of DNA prepared from paraffin-embedded samples. Nevertheless, using a method for the statistical evaluation of the balanced state for each individual experiment, we were able to reveal imbalances with high significance, which were in good concordance with previous data collected by chromosomal CGH from the same patients. Owing to the improved resolution of matrix-CGH, genomic imbalances could be narrowed down to the level of individual bacterial artificial chromosome and P1-derived artificial chromosome clones. On average 37 gains and 13 losses per tumor cell genome were scored. Gains in more than 30% of the cases were found on 1p, 1q, 6p, 7p, 8q, 9q, 11q, 12q, 17p, 17q, 20q, and 22q, and losses on 6q, 9p, 11q, and 17p. Of the 51 chromosomal regions found amplified by matrix-CGH, only 12 had been identified by chromosomal CGH. Within these 51 amplicons, genome database information defined 112 candidate genes, 44 of which were validated by either PCR amplification of sequence tag sites or DNA sequence analysis.
Nessling
Michelle
M
Abteilung Molekulare Genetik, Deutsches Krebsforschungszentrum and Pathologisches Institut, Universität Heidelberg, Heidelberg, Germany.
Richter
Karsten
K
Schwaenen
Carsten
C
Roerig
Peter
P
Wrobel
Gunnar
G
Wessendorf
Swen
S
Fritz
Björn
B
Bentz
Martin
M
Sinn
Hans-Peter
HP
Radlwimmer
Bernhard
B
Lichter
Peter
P
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D005260:Female; D005557:Formaldehyde; D042822:Genomic Instability; D006801:Humans; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D016612:Paraffin Embedding; D016707:Tissue Fixation
D005557:Formaldehyde