Detection by fluorescence in situ hybridization of microdeletions at 1p36 in lymphomas, unidentified on cytogenetic analysis.
The chromosomal band 1p36 exhibits frequent loss of heterozygosity in a variety of human malignancies, suggesting the presence of an as yet unidentified tumor suppressor gene. The faint terminal subbands often make cytogenetic analysis of 1p36 particularly difficult. Small deletions at this locus may therefore escape detection on analysis by conventional cytogenetics, a hypothesis that we have explored using fluorescence in situ hybridization (FISH) in malignant lymphoma. The study cohort consisted of 20 cases of lymphoma of various subtypes without any 1p abnormality on G-banded karyotyping. FISH was performed using a human chromosome 1 paint and a bacterial artificial chromosome probe RP4-755G5 localizing to 1p36.33, the most telomeric subband of 1p36. Tumors demonstrating 1p36.33 deletions were additionally analyzed by FISH using a second probe from the proximal 1p36.1 subband, to further define the breakpoint. Eight cases of follicular lymphoma (FL), 5 diffuse large B-cell lymphomas (DLBCL), 2 Hodgkin disease, 2 B-cell small lymphocytic lymphomas, 2 T-cell lymphomas, and 1 marginal zone lymphoma were analyzed. FISH identified deletions at 1p36.33 in 5 of the 20 cases: 3 DLBCL and 2 FL. FISH is considerably more sensitive for identifying lymphoma genetic alterations than conventional cytogenetics. Deletion of the distal part of the 1p36 may be a much more common aberration than previously recognized in lymphoma.
Rajgopal
Achuthan
A
Molecular Medicine Unit, St. James's University Hospital, Leeds LS9 7TF, UK.
Carr
Ian M
IM
Leek
Jack P
JP
Hodge
Donald
D
Bell
Sandra M
SM
Roberts
Paul
P
Horgan
Kieran
K
Bonthron
David T
DT
Selby
Peter J
PJ
Markham
Alexander F
AF
MacLennan
Kenneth A
KA
D000293:Adolescent; D000328:Adult; D000368:Aged; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008223:Lymphoma / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity