Deletion analysis of the p16 tumor suppressor gene in gastrointestinal mucosa-associated lymphoid tissue lymphomas.

BACKGROUND & AIMS: The molecular mechanisms responsible for initiation and progression of gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphomas are largely unknown. The aim of this study was to analyze the p16 tumor suppressor gene in MALT lymphomas of the stomach and colon.

METHODS

Tumor samples were obtained from 28 patients with low-grade (n = 12) and high-grade (n = 14) gastric MALT lymphomas and from 2 patients with colonic MALT lymphomas. DNA was extracted from microdissected areas with at least 80% tumor cells. To detect homozygous p16 deletions, a semiquantitative polymerase chain reaction assay was used, whereby either p16 exon 1 or exon 2 was coamplified with an unrelated sequence as internal control.

RESULTS

Homozygous p16 deletions were found in 2 of 14 (14%) cases with high-grade gastric MALT lymphomas. Both patients had Helicobacter pylori-associated gastritis; however, DNA extracted from areas of gastritis showed a normal p16 complement. No deletion was found in any of the low-grade gastric or the colonic MALT lymphoma specimens.

CONCLUSIONS

In a subset of gastric MALT lymphomas, homozygous p16 deletions are acquired and may contribute to the transformation from a low-grade to a high-grade malignancy.