Genome-wide-array-based comparative genomic hybridization reveals genetic homogeneity and frequent copy number increases encompassing CCNE1 in fallopian tube carcinoma.
Fallopian tube carcinoma (FTC) is a rare, poorly studied and aggressive cancer, associated with poor survival. Since tumorigenesis is related to the acquisition of genetic changes, we used genome-wide array comparative genomic hybridization to analyse copy number aberrations occurring in FTC in order to obtain a better understanding of FTC carcinogenesis and to identify prognostic events and targets for therapy. We used arrays of 2464 genomic clones, providing approximately 1.4 Mb resolution across the genome to map genomic DNA copy number aberrations quantitatively from 14 FTC onto the human genome sequence. All tumors showed a high frequency of copy number aberrations with recurrent gains on 3q, 6p, 7q, 8q, 12p, 17q, 19 and 20q, and losses involving chromosomes 4, 5q, 8p, 16q, 17p, 18q and X. Recurrent regions of amplification included 1p34, 8p11-q11, 8q24, 12p, 17p13, 17q12-q21, 19p13, 19q12-q13 and 19q13. Candidate, known oncogenes mapping to these amplicons included CMYC (8q24), CCNE1 (19q12-q21) and AKT2 (19q13), whereas PIK3CA and KRAS, previously suggested to be candidate driver genes for amplification, mapped outside copy number maxima on 3q and 12p, respectively. The FTC were remarkably homogeneous, with some recurrent aberrations occurring in more than 70% of samples, which suggests a stereotyped pattern of tumor evolution.
Snijders
Antoine M
AM
Cancer Research Institute, University of California San Francisco, San Francisco, CA, USA.
Nowee
Marlies E
ME
Fridlyand
Jane
J
Piek
Jurgen M J
JM
Dorsman
Josephine C
JC
Jain
Ajay N
AN
Pinkel
Daniel
D
van Diest
Paul J
PJ
Verheijen
René H M
RH
Albertson
Donna G
DG
D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D019927:Cyclin E; D004247:DNA / Q000378:metabolism; D005185:Fallopian Tube Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*
C475820:CCNE1 protein, human; D019927:Cyclin E; D015513:Oncogene Proteins; D004247:DNA