Common and distinct genomic events in sporadic colorectal cancer and diverse cancer types.
Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality, and elucidation of its underlying genetics has advanced diagnostic screening, early detection, and treatment. Because CRC genomes are characterized by numerous non-random chromosomal structural alterations, we sought to delimit regions of recurrent amplifications and deletions in a collection of 42 primary specimens and 37 tumor cell lines derived from chromosomal instability neoplasia and microsatellite instability neoplasia CRC subtypes and to compare the pattern of genomic aberrations in CRC with those in other cancers. Application of oligomer-based array-comparative genome hybridization and custom analytic tools identified 50 minimal common regions (MCRs) of copy number alterations, 28 amplifications, and 22 deletions. Fifteen were highly recurrent and focal (<12 genes) MCRs, five of them harboring known CRC genes including EGFR and MYC with the remaining 10 containing a total of 65 resident genes with established links to cancer. Furthermore, comparisons of these delimited genomic profiles revealed that 22 of the 50 CRC MCRs are also present in lung cancer, glioblastoma, and/or multiple myeloma. Among 22 shared MCRs, nine do not contain genes previously shown genetically altered in cancer, whereas the remaining 13 harbor 35 known cancer genes, of which only 14 have been linked to CRC pathogenesis. Together, these observations point to the existence of many yet-to-be discovered cancer genes driving CRC development, as well as other human cancers, and show the utility of high-resolution copy number analysis in the identification of genetic events common and specific to the development of various tumor types.
Martin
Eric S
ES
Department of Medical Oncology, Belfer Institute for Innovative Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Tonon
Giovanni
G
Sinha
Raktim
R
Xiao
Yonghong
Y
Feng
Bin
B
Kimmelman
Alec C
AC
Protopopov
Alexei
A
Ivanova
Elena
E
Brennan
Cameron
C
Montgomery
Kate
K
Kucherlapati
Raju
R
Bailey
Gerald
G
Redston
Mark
M
Chin
Lynda
L
DePinho
Ronald A
RA
D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D016678:Genome; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008957:Models, Genetic; D009154:Mutation; D009693:Nucleic Acid Hybridization; D017422:Sequence Analysis, DNA