p53 mutations are associated with histologic transformation of follicular lymphoma.
The majority of low-grade non-Hodgkin's lymphomas (NHL) undergo clinical progression toward intermediate- and high-grade lymphomas. This progression is often associated with histologic transformation from follicular to diffuse-type NHL. The pathogenetic mechanisms underlying this evolution are presently unknown. In this study, we have analyzed the role in NHL progression of relevant genetic lesions affecting proto-oncogenes and tumor suppressor genes. Sequential biopsies from 21 patients with clinical progression with (5 cases) or without (16 cases) evidence of histologic transformation were analyzed for karyotypic changes, c-myc rearrangements and deletions affecting 6q27 by Southern blot analysis, and p53 mutations by single-strand conformation polymorphism (SSCP) analysis coupled with direct sequencing of polymerase chain reaction-amplified products. No novel cytogenetic aberration was detected in association with progression, and all samples analyzed displayed a normal c-myc gene. Mutations of the p53 gene were detected in 4 of 5 cases displaying histologic transformation from follicular to diffuse-type NHL and in none of the 16 cases displaying clinical progression in the absence of histologic transformation. In 1 of these positive cases, the same mutation was also present in the pretransformation biopsy, correlating with the presence of diffuse-type areas within a predominant follicular pattern. In 1 of these cases, a deletion of 6q27 was also detected in the posttransformation biopsy along with a p53 mutation. These findings indicate that p53 mutations are associated with and may be responsible for histologic transformation of follicular lymphoma.
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
F
F
Lo Coco
G
G
Gaidano
D C
DC
Louie
K
K
Offit
R S
RS
Chaganti
R
R
Dalla-Favera
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D005260:Female; D017353:Gene Deletion; D016259:Genes, myc; D016158:Genes, p53; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation