Molecular mapping of chromosome 2 deletions in murine radiation-induced AML localizes a putative tumor suppressor gene to a 1.0 cM region homologous to human chromosome segment 11 p 11-12

Andrew Silver*, John Moody, Rosemary Dunford, Debbie Clark, Sue Ganz, Robert Bulman, Simon Bouffler, Paul Finnon, Emmy Meijne, Rene Huiskamp, Roger Cox

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

Abstract

Radiation-induced acute myeloid leukemias (AMLs) in the mouse are characterized by chromosome 2 deletions. Previous studies showed that a minimal deleted region (mdr) of ~6.5 cM is lost from one homologue in chromosome 2-deleted AMLs. An AML tumor suppressor gene is proposed to map within this mdr. In this study, we refine the mdr to a 1 cM interval between markers D2Mit126 and D2Mit185 by microsatellite analysis of 21 primary radiation-induced F1 AMLs. The construction of a partial yeast artificial chromosome (YAC) contig spanning the mdr and the location of six known genes indicated that the 1 cM mdr is homologous to human 11p11-12, a region implicated in some human AMLs. Screening of five cell lines derived from primary radiation-induced AMLs for homozygous loss of microsatellites and genes mapping within the mdr revealed loss of both copies of the hemopoietic tissue-specific transcription factor Sfpil (PU.1/Spil) in one cell line. Studies of primary and F1 AMLs failed to implicate Sfpil as the AML tumor suppressor gene. YAC contig construction, together with data suggesting that the critical gene flanks Sfpil, represents significant progress toward identifying an AML tumor suppressor gene.

Original languageEnglish
Pages (from-to)95-104
Number of pages10
JournalGenes Chromosomes and Cancer
Volume24
Issue number2
DOIs
Publication statusPublished - Feb 1999

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