MOLECULAR-CLONING AND EXPRESSION ANALYSIS OF 5 NOVEL GENES IN CHROMOSOME 1P36

The human chromosome 1p36 region displays frequent nonrandom chromosom al deletions and translocations in a number. of human malignancies; th ese are thought to inactivate tumor suppressor genes. To identify thes e putative tumor suppressors we employed exon trapping, cDNA selection , and zoo blot analysis to clone five new genes located in 1p36. Two o f these represent novel genes and were designated C1orf1 and xylan 1,4 -beta-xylosidase 1 (XBX1). Two further genes represented new members o f known gene families: PTPRZ2 was a tyrosine phosphatase and FRAP2 rep resented a FKBP12-rapamycin-associated protein. The fifth gene identif ied, ENO1L1, was significantly homologous to c-myc promoter binding pr otein, MBP-1, and to enolase 1 (ENO1), It colocalized with alpha enola se (ENO1) on a single pi clone. ENO1L1 differed from both ENO1 and MBP -1 in the organization of its 5' untranslated sequences. Second, MBP-1 contained two single-base insertions not present in either ENO1 or EN O1L1 sequences, which led to a shift in the MBP-1 reading frame. Expre ssion analysis revealed two brain-specific transcripts of 7.9 and 6.5 kb for PTPRZ2, In contrast, C1orf1, FRAPS, ENO1L1, and XBX1 appeared t o be expressed ubiquitously in the tissues tested, with transcript siz es of 4.5, 8.7, 1.75, and 4.5 kb, respectively, Using fluorescence in situ hybridization, we mapped the five novel genes relative to chromos ome 1p36 breakpoints present in three established tumor cell lines and one nontumor cell line. The karyotypic abnormalities in these cell li nes were exploited as chromosomal landmarks; we could thus show that t he telomere to centromere gene order was PTPRZ2-(MBP-1/ENO1/ENO1L1)-(C 1orf1/XBX1)-FRAP2. The localization of these genes to a chromosomal re gion that is prone to deletions in human cancers makes them potential candidate tumor suppressors. (C) 1998 Academic Press.