Identification of chromosomal aberrations of metastatic potential in colorectal carcinoma.
In colorectal cancer (CRC) care, treatment decisions depend on the efforts to estimate the metastatic potential of tumors. The liver is one of the most common metastatic sites of CRC and the prognosis of CRC patients often reflects metastases to distant sites. To identify chromosomal aberrations associated with liver metastasis, we performed allelic copy number analysis for CRC with or without synchronous liver metastasis using genotyping arrays. By allelic copy number analysis of CRC samples, we observed common aberrations in 14 chromosomal arms in two groups, that is, gains on 7p22.3-p11.2, 8q22.3-q24.3, 13q12.12-q34, and 20q11.22-q13.33 and loss of heterozygosity (LOH) on 4q12-q35.1, 5q11.2-q35.3, 8p23.3-p12, 15q11.2-q26.3, 17p13.3-p11.2, 17q11.2-q25.1, 18p11.32-p11.21, 18q11.2-q23, 20p13-p12.1, and 22q11.1-q13.32. We found that gains on 20p13-p12.1 and 20q11.21-q13.33 and LOH on 6q14.1-q25.1 were more frequent in CRC with liver metastasis. We also compared chromosomal aberrations in primary CRC lesions with those of the corresponding liver metastasis and found that the allelic genome imbalance status of a metastatic lesion is similar to that of the primary cancer, which suggests that chromosomal aberrations are largely maintained on hematogenous spread. Intriguingly, several chromosomal aberrations in CRC were found in the primary cancer but not in the corresponding liver metastasis, thus suggesting heterogeneity of cancer cells within solid tumors or the presence of events uniquely developed in primary tumors. Consequently, CRC with and without liver metastasis harbor similar chromosomal aberrations, and chromosomal aberration at 6q, 20p, and 20q may be involved in the process of liver metastasis of CRC.
Yamamoto
Shogo
S
Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Tokyo, Japan.
Midorikawa
Yutaka
Y
Morikawa
Teppei
T
Nishimura
Yoji
Y
Sakamoto
Hirohiko
H
Ishikawa
Shumpei
S
Akagi
Kiwamu
K
Aburatani
Hiroyuki
H
D000368:Aged; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis