Recurrent deletions involving chromosomes 1, 5, 17, and 18 in colorectal carcinoma: possible role in biological and clinical behavior of tumors.
Academic Article
Overview
abstract
We have employed cytogenetic and restriction fragment length polymorphism (RFLP) analysis to identify a full spectrum of cytogenetic and molecular alterations associated with initiation and progression of "sporadic" colorectal cancer and also to correlate the alterations with biological and clinical behavior of the tumors. The study series included 63 colorectal cancers, 47 primary and 16 metastatic recurrences. Cytogenetic analysis was successful in 48 tumors (76%) of which 44 (91%) were abnormal. Of these 44 tumors, clonal abnormalities were identified in 43, whereas chromosomes from one tumor were unsuitable for complete analysis. Each of these abnormal tumors displayed heterogeneity with regard to extent and complexity of recurrent chromosomal abnormalities. Numerical losses of chromosomes 17 and 18 (20-34%) and gains of chromosome 7 (28%) were significantly higher. The four most frequent structural rearrangements on the other hand, involved specific regions of chromosomes 1p, 5q, 17p, and 18q. The shortest regions of overlap of these rearrangements or losses were located at 1p36, 5q21-22, 17p13 and 18q21- > ter. RFLP analysis directed at 1p, 5q, 17p and 18q identified allelic deletions of these regions in 39 tumors (64%) which included 17 normal and 11 cytogenetic failures. Of all the informative tumors, 32%, 37%, 31%, and 63% showed allelic losses at chromosomes 1p, 5q, 17p and 18q respectively. The two methods of analysis (cytogenetics and RFLP) employed to identify genetic alterations were complementary; probes for chromosome 1 and 18 showed the greatest degree of concordance, whereas probes for chromosomes 5 and 17 provided relatively higher rate of discordance with cytogenetic results. These differences could be attributed mainly to three reasons: 1) a limited number of probes used for RFLP analysis; 2) contamination of tumor cells with normal cells, and 3) either mutational inactivation or deletion of specific alleles not closely linked to the probes used. Regardless of these limitations, however, the combined use of cytogenetic and RFLP identified genetic alterations in a large number of tumors and help elucidate the role of hyperdiploidy and/or relative deficiency of a given chromosomal segment in expression of recessive mutations. In addition, alterations of either chromosomes 1 or 17 predicted poorer survival for the patients with primary colorectal cancer (p = 0.03).
