Peutz-Jeghers polyps, dysplasia, and K-ras codon 12 mutations

Abstract

Background: Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant, polyposis syndrome, associated with an increased risk of gastrointestinal and extragastrointestinal malignancy. Occasionally dysplasia occurs in PJS polyps.

Aims: In colorectal carcinomas, mutations in codon 12 of the K-ras oncogene are common and are found at similar frequency in precursor adenomas. Therefore, K-ras codon 12 point mutations in PJS polyps, were evaluated.

Materials and methods: Fifty two PJS polyps, including four with dysplasia, collected from 19 patients with PJS, were analysed for mutations in the K-ras codon 12 by a mutant enriched polymerase chain reaction procedure, followed by allele specific oligodeoxynucleotide hybridisation.

Results: A K-ras codon 12 mutation was identified, in one colonic polyp with dysplasia. The mutation was found in the non-neoplasmic epithelial cells and not in the dysplastic component of the polyp.

Conclusions: K-ras codon 12 point mutations are very rare in PJS polyps, by contrast with colorectal adenomas. The findings support previous evidence that there seems to be no intrinsic relation between K-ras codon 12 mutation and dysplasia.

Figure 1

: (A) Non-dysplastic and (B) dysplastic microscopic sections from the PJS polyp positive for a K-ras codon 12 mutation. This polyp shows heterogeneity for the K-ras mutation with the mutation solely found in the non-dysplastic section (haematoxylin and eosin).

Figure 2

: Autoradiograph of K-ras codon 12 point mutation analysis in PJS polyps. Left column of the panels: mutant unenriched PCR products. Right column: mutant enriched PCR products. Row 1, positive control for wild type K-ras codon 12 (left column), positive controls for wild type K-ras codon 12, Arg mutant K-ras, and Val mutant K-ras (right column), respectively. Rows 2 and 3, PCR products from dysplastic section of the polyp with K-ras mutation (in duplicate). Rows 4 and 5, PCR products of non-dysplastic section (in duplicate). Row 6, PCR product of PJS polyp negative for K-ras codon 12 mutation. Row 7, PCR products from the entire PJS polyp positive for the K-ras mutation. Row 8, positive (placenta DNA) PCR control. Row 9, buffer only (negative) PCR control.