RECURRENT DELETIONS INVOLVING CHROMOSOME-1, CHROMOSOME-5, CHROMOSOME-17, AND CHROMOSOME-18 IN COLORECTAL-CARCINOMA - POSSIBLE ROLE IN BIOLOGICAL AND CLINICAL BEHAVIOR OF TUMORS
H. Gerdes et al., RECURRENT DELETIONS INVOLVING CHROMOSOME-1, CHROMOSOME-5, CHROMOSOME-17, AND CHROMOSOME-18 IN COLORECTAL-CARCINOMA - POSSIBLE ROLE IN BIOLOGICAL AND CLINICAL BEHAVIOR OF TUMORS, Anticancer research, 15(1), 1995, pp. 13-24
We have employed cytogenetic and restriction fragment length polymorph
ism (RFLP) analysis to identify a full spectrum of cytogenetic and mol
ecular alterations associated with initiation and progression of ''spo
radic'', colorectal cancer and also to correlate the alterations with
biological and clinical behavior of the tumors. The study series inclu
ded 63 colorectal cancers, 47 primary and 16 metastatic recurrences. C
ytogenetic analysis was successful in 48 tumors (76%) of which 44 (91%
) were abnormal. Of these 44 tumors, clonal abnormalities were identif
ied in 43, whereas chromosomes from one tumor were unsuitable for comp
lete analysis. Each of these abnormal tumors displayed heterogeneity w
ith regard to extent and complexity of recurrent chromosomal abnormali
ties. Numerical losses of chromosomes 17 and 18 (20-34%) and gains of
chromosome 7 (28%) were significantly higher. The four most frequent s
tructural rearrangements on the other hand, involved specific regions
of chromosomes 1p, 5q, 17p, and 18q. The shortest regions of overlap o
f these rearrangements or losses were located at 1p36, 5q21-22, 17p13
and 18q21->ter. RFLP analysis directed at Ip, 5q, 17p and 18q identifi
ed allelic deletions of these regions in 39 tumors (64%) which include
d 17 normal and If 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 an
d RFLP) employed to identify genetic alterations were complementary, p
robes for chromosome 1 and 18 showed the greatest degree of concordanc
e, 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 u
sed for RFLP analysis; 2) contamination of tumor cells with normal cel
ls, and 3) either mutational inactivation or deletion of specific alle
les not closely linked to the probes used. Regardless of these limitat
ions, however, the combined use of cytogenetic and RFLP identified gen
etic alterations in a large number of tumors and help elucidate the ro
le 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 patie
nts with primary colorectal cancer (p=0.03).