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5'-CpG island methylation of the LKB1/STK11 promoter and allelic loss at chromosome 19p13.3 in sporadic colorectal
J Trojan1, A Brieger, J Raedle
1Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt a.M., Germany.
Gut
|July 18, 2000
Summary
Genetic and epigenetic inactivation of the LKB1/STK11 tumor suppressor gene is rare in sporadic colorectal cancer. Loss of heterozygosity (LOH) at 19p13.3 correlates with advanced stage and left-sided tumors.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Peutz-Jeghers syndrome (PJS) is linked to germline mutations in the LKB1/STK11 gene.
- LKB1/STK11 is considered a tumor suppressor due to loss of heterozygosity (LOH) in PJS hamartomas.
- The frequency of LKB1/STK11 inactivation in sporadic tumors is not well understood.
Purpose of the Study:
- Investigate LKB1/STK11 promoter hypermethylation in sporadic colorectal cancer.
- Analyze allelic loss at the LKB1/STK11 locus in sporadic colorectal cancer specimens.
Main Methods:
- DNA extraction from 50 sporadic colorectal adenocarcinomas and normal tissue.
- Methylation-specific PCR (MSP) to analyze LKB1/STK11 promoter 5'-CpG island methylation.
- Analysis of chromosome 19p13.3 LOH and sequencing of LKB1/STK11 in tumors with LOH.
Main Results:
- LKB1/STK11 promoter hypermethylation occurred in 8% of analyzed tumors.
- LOH at 19p13.3 was observed in 13% of informative tumors.
- LOH was associated with advanced tumor stage and left-sided location; no correlation with hypermethylation or somatic mutation.
Conclusions:
- LKB1/STK11 promoter hypermethylation and allelic loss are infrequent in sporadic colorectal cancer.
- LOH at 19p13.3 is linked to advanced stage and left-sided tumor location.
- No direct association found between LOH, LKB1/STK11 promoter hypermethylation, or somatic mutation in this cohort.
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