High frequency of genetic aberrations in enteropathy-type T-cell lymphoma.
To define genetic aberrations playing a role in the development of enteropathy-type T-cell lymphoma (ETL), we examined 26 such tumors using a battery of 47 microsatellite markers. The most frequent aberration (seen in 40% of informative genotypes) was amplification of genomic material in region 9q34 encompassing c-abl and Notch-1 gene loci. Other frequent amplifications were detected in regions 5q33.3-34 and 7q31 (both in more than 30%). Multiple losses of heterozygosity were detected in 6p24, 7p21, 17q23-25, regions containing putative tumor suppressor genes, and in the p53 locus in 17p13.1. Analysis of the pattern of occurrence of these aberrations revealed existence of two ETL subgroups: one of them characterized by the 9q34 aberration and another smaller one showing allelic imbalances in 3q27. These two aberrations were mutually exclusive. Microsatellite instability (MSI) was detected in 69% of the examined lymphomas; the percentage of MSI-positive genotypes per tumor ranged from 2% to 12%. The spectrum of genetic alterations detected showed patterns dependent on morphology. Monomorpic ETLs displayed frequently biallelic TCR-gamma gene rearrangement (p = 0078, chi(2) test). They showed a different pattern and fewer allelic imbalances (no 3q27, 4q28, 13q14, fewer 5q21, or 5q33.3-34 aberrations) and a lower frequency of MSI than pleomorphic ETLs.
Baumgärtner
Anne K
AK
Institute of Pathology, Würzburg University, Würzburg, Germany.
Zettl
Andreas
A
Chott
Andreas
A
Ott
German
G
Müller-Hermelink
Hans Konrad
HK
Starostik
Petr
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005784:Gene Amplification; D015329:Gene Rearrangement, T-Lymphocyte; D005838:Genotype; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm