Evaluation of 1p losses in primary carcinomas, local recurrences and peripheral metastases from colorectal cancer patients.
Cytogenetic and molecular genetic analyses of colorectal adenomas and carcinomas have shown that loss of the distal part of chromosome arm 1p is common, particularly in tumors of the left colon. Because the importance of 1p loss in colorectal cancer metastases is unknown, we compared the frequency, exact site and extent of 1p deletions in primary carcinomas (n=28), local recurrences (n=19) and metastases (n=33) from 67 colorectal cancer patients using 14 markers in an allelic imbalance study. Loss of 1p was found in 50% of the primary carcinomas, 33% of the local recurrences, and 64% of the metastases, revealing a significant difference between the local recurrences and the metastases (P=.04). The smallest region of 1p deletion overlap (SRO) defined separately for each group of lesions had the region between markers D1S2647 and D1S2644, at 1p35-36, in common. The genes PLA2G2A (1p35.1-36) and TP73 (1p36.3) were shown to lie outside this consistently lost region, suggesting that neither of them are targets for the 1p loss. In the second part of the study, microdissected primary carcinomas and distant metastases from the same colorectal cancer patients (n=18) were analyzed, and the same 1p genotype was found in the majority of patients (12/18, 67%). The finding that primary carcinoma cells with metastatic ability usually contain 1p deletions, and that some cases lacking 1p alterations in the primary tumor acquire such changes during growth of a metastatic lesion, supports the notion that 1p loss may be important both early and late in colorectal carcinogenesis, with the apparent exception of local recurrences.
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway.
L
L
Thorstensen
H
H
Qvist
S
S
Heim
G J
GJ
Liefers
J M
JM
Nesland
K E
KE
Giercksky
R A
RA
Lothe
D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000302:isolation & purification; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000556:secondary; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D004273:DNA, Neoplasm