6767

ST13

AAG2|FAM10A1|FAM10A4|HIP|HOP|HSPABP|HSPABP1|P48|PRO0786|SNC6;suppression of tumorigenicity 13 (colon carcinoma) (Hsp70 interacting protein);ST13;suppression of tumorigenicity 13 (colon carcinoma) (Hsp70 interacting protein)

Hsp70-interacting protein|aging-associated protein 2|heat shock 70kD protein binding protein|hsc70-interacting protein|progesterone receptor-associated p48 protein|putative tumor suppressor ST13|renal carcinoma antigen NY-REN-33|suppression of tumorigenic

22q13.2

protein-coding

Count: 2; TAG,Generif

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 approximately 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 I cM interval between markers D2Mit126 and D2Mit185 by microsatellite analysis of 21 primary radiation-induced F I 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 Sfpi1(PU.1/Spi1) in one cell line. Studies of primary and F1 AMLs failed to implicate Sfpi1 as the AML tumor suppressor gene. YAC contig construction, together with data suggesting that the critical gene flanks Sfpi1, represents significant progress toward identifying an AML tumor suppressor gene.

Using the 650-kb DNA sequence from the minimally deleted region in B-cell chronic lymphocytic leukemia (BCLL), we have identified a new gene, FAM10A4, that maps to the proximal end of the region. This gene has been shown to be part of a now six-member family of genes with high homology to the ST13 tumor suppressor gene. We have established conditions to specifically undertake mutation studies of the chromosome 13 member of this family and have identified a Ser71Leu change in BCLL samples, which is apparently a polymorphism. The characterization of this gene will permit mutation studies in other tumor cell types such as multiple myeloma and prostate cancer, which also show genetic loss in the 13q14 region.