Chromosome copy number analysis in screening for prognosis-related genomic regions in colorectal carcinoma.
Colorectal carcinoma (CRC) remains the major cause of cancer death in humans. Although chromosomal structural anomaly is presumed to play an important role in the carcinogenesis of CRC, chromosomal copy number alterations (CNA) and loss of heterozygosity (LOH) have not yet been analyzed extensively at high resolution in CRC. Here we aim to identify recurrent CNA and LOH in human CRC with the use of single nucleotide polymorphism-typing microarrays, and to reveal their relevance to clinical outcome. Surgically resected CRC specimens and paired normal mucosa were obtained from a consecutive series of 94 patients with CRC, and both of them were subjected to genotyping with Affymetrix Mapping 50K arrays. CNA and LOH were inferred computationally on every single nucleotide polymorphism site by integrating the array data for paired specimens. Our large dataset reveals recurrent CNA in CRC at chromosomes 7, 8, 13, 18, and 20, and recurrent LOH at chromosomes 1p, 4q, 5q, 8p, 11q, 14q, 15q, 17p, 18, and 22. Frequent uniparental disomy was also identified in chromosomes 8p, 17p, and 18q. Very common CNA and LOH were present at narrow loci of <1 Mbp containing only a few genes. In addition, we revealed a number of novel CNA and LOH that were linked statistically to the prognosis of the patients. The precise and large-scale measurement of CNA and LOH in the CRC genome is efficient for pinpointing prognosis-related genome regions as well as providing a list of unknown genes that are likely to be involved in CRC development.
Division of Functional Genomics, Jichi Medical University, Tochigi 329-0498, Japan.
Kentaro
K
Kurashina
Yoshihiro
Y
Yamashita
Toshihide
T
Ueno
Koji
K
Koinuma
Jun
J
Ohashi
Hisanaga
H
Horie
Yasuyuki
Y
Miyakura
Toru
T
Hamada
Hidenori
H
Haruta
Hisashi
H
Hatanaka
Manabu
M
Soda
Young Lim
YL
Choi
Shuji
S
Takada
Yoshikazu
Y
Yasuda
Hideo
H
Nagai
Hiroyuki
H
Mano
D000782:Aneuploidy; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D016678:Genome; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008403:Mass Screening; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis