Refinement of the commonly deleted segment in myeloid leukemias with a del(20q).
A deletion of the long arm of chromosome 20 [del(20q)] is a recurring abnormality in a wide spectrum of myeloid disorders. Loss of genetic material from 20q may confer a proliferative advantage to myeloid cells, possibly through loss of function of a tumor suppressor gene. Previously, we analyzed leukemia cells from 19 patients with a del(20q) by fluorescence in situ hybridization (FISH) and identified a segment that was deleted in 95% of all patients examined. The deleted interval extended from 20q11.2 to q12, spanned approximately 13 Mb, and was flanked proximally by RPN2 and distally by D20S17. To narrow the commonly deleted segment and facilitate the identification of candidate genes, we have employed molecular approaches in combination with FISH. By using 21 microsatellite markers positioned in a recently generated physical map of 20q, we performed allele loss studies in myeloid leukemia cells from 23 patients with a del(20q). The results of these studies allowed us to delineate a new proximal border, flanked by marker D20S206. By FISH analysis of additional leukemia samples from patients with a del(20q), we have also delineated a new distal boundary between markers D20S119 and UT654. As a result of the redesignation of both the proximal and distal boundaries, we have successfully narrowed the commonly deleted segment within 20q12 to a region spanning approximately 8 Mb. Identification of the smallest deleted segment will facilitate the eventual cloning of a candidate myeloid tumor suppressor gene.
Wang
P W
PW
Section of Hematology/Oncology, University of Chicago, Illinois 60637, USA. pwwang@mcis.bsd.uchicago.edu
Iannantuoni
K
K
Davis
E M
EM
Espinosa
R
R
Stoffel
M
M
Le Beau
M M
MM
D000483:Alleles; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002876:Chromosomes, Bacterial; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000235:genetics*; D018895:Microsatellite Repeats