Allelic imbalance at NBS1 is frequent in both proximal and distal colorectal carcinoma.
Nijmegen breakage syndrome (NBS) is a hereditary disorder involving chromosomal instability, cancer risk and radiosensitivity. NBS carriers have an increased risk of cancer, though the significance of mutations in the NBS1 gene in sporadic cancer has not yet been investigated. Because the loss of NBS1 is associated with increased chromosomal re-arrangements, and tumors of the colon are particularly prone to chromosomal anomalies, we have begun to study the NBS1 locus in colorectal cancer (CRC). DNA was isolated from 99 microdissected colorectal tumors, and microsatellite markers flanking the NBS1 locus at 8q21.3 as well as elsewhere on 8q were analyzed. Normal lymphocyte DNA from each patient served to normalize the amplification of each allele, and a reduction of at least 35% in the intensity of one allele was taken as evidence of allelic imbalance (AI). In proximal and distal CRCs we found 25.9 and 36.2% with AI at 8q21.3, respectively. AI in proximal CRC tended not to extend to marker D8S555 at 8q24.1, whereas in distal CRC the region of AI frequently included all the informative markers. AI of 8q21.3 was not associated with any clinical variable. These results suggest that 8q21.3 contains a tumor suppressor gene involved in proximal CRC, possibly NBS1. The large regions of AI make it difficult to determine the importance of AI at the NBS1 locus in distal CRC.
Uhrhammer
N
N
Centre Jean Perrin, 63011 Clermont-Ferrand, France.
Bay
J O
JO
Gosse-Brun
S
S
Kwiatkowski
F
F
Rio
P
P
Daver
A
A
Bignon
Y J
YJ
D000483:Alleles; D018797:Cell Cycle Proteins / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8; D003106:Colon / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D016147:Genes, Tumor Suppressor; D006801:Humans; D018895:Microsatellite Repeats; D009687:Nuclear Proteins
D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins