Loss of heterozygosity on chromosome 10q is associated with earlier onset sporadic colorectal adenocarcinoma.
Recent studies have shown that loss of heterozygosity (LOH) on chromosome 10q is a frequent event in a number of tumour types including colorectal cancers. Because previous studies have used markers located mainly distally on chromosome 10, we have examined 114 sporadic colorectal adenocarcinomas for LOH using a panel of 9 highly polymorphic microsatellite markers spanning the long arm of chromosome 10. Using microdissected tumour material, LOH of one or more chromosome 10q markers was a frequent event (75 of 114; 66%). The highest frequency of loss (42 of 96; 44%) was observed at the marker D10S1790 located at 10q21.1. The mean age of presentation, of patients with LOH of D10S1790 was significantly (p = 0.0006) lower (67.1 years) compared to patients with retention of this marker (73.5 years). When we compared frequency of loss at this marker in patients presenting before 70 years of age (68%) to those above 70 years (23%) we observed a significant difference (p < 0.0001). Statistical analysis between loss, or instability at other markers and clinicopathological features did not show any significant associations. In addition LOH at D10S1790 was infrequent in adenomas (2 of 20; 10%) compared to adenocarcinomas (42 of 96; 44%) (p = 0.0047), suggesting that loss within this region is a late event in colorectal tumorigenesis. The association of loss at D10S1790 and an earlier age of presentation in adenocarcinomas suggests that this locus may harbor a tumour suppressor gene(s), which affects the rate of colorectal tumour progression. Identification of this region of genetic loss further refines our understanding of the paradigm in this tumour type of multiple-steps responsible for initiation and progression.
Centre for Cell and Molecular Medicine, School of Postgraduate Medicine, Keele University, North Staffordshire Hospital, Stoke-on-Trent, United Kingdom.
Adeshina S
AS
Fawole
David J
DJ
Simpson
Ramesh
R
Rajagopal
Jackie
J
Elder
Tracey A
TA
Holland
Anthony
A
Fryer
Mark
M
Deakin
James B
JB
Elder
William E
WE
Farrell
D000230:Adenocarcinoma / Q000235:genetics*; D000236:Adenoma / Q000235:genetics*; D000368:Aged; D002471:Cell Transformation, Neoplastic; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics; D009367:Neoplasm Staging
D004273:DNA, Neoplasm