title: Cloning of two candidate tumor suppressor genes within a 10 kb region on chromosome 13q14, frequently deleted in chronic lymphocytic leukemia.
abstract: Previous studies have indicated the presence of a putative tumor suppressor gene on chromosome 13q14, commonly deleted in patients with B-cell chronic lymphocytic leukemia (B-CLL). We have previously defined a minimally deleted region of 130 kb centromeric to the marker D13S272, and constructed a PAC and cosmid contig encompassing this area. In the present study we have made a detailed restriction and transcriptional map of the region of interest. Using these tools we have screened a panel of 206 primary CLL clones and three cell lines. In five CLL cases we found limited deletions defining the region of interest to an area of no more than 10 kb. Two adjacent genes, termed Leu1 and Leu2 (leukemia-associated gene 1 and 2), were mapped to the minimally deleted region, with several patients showing deletion borders within these genes. The Leu1 and Leu2 genes show little homology to previously published genes at the nucleotide and expected translated amino acid sequence level. Mutational analysis of the Leu1 and 2 genes in 170 CLL samples revealed no small intragenic mutations or point mutations. However, in all cases of 13q14 loss examined, the first exon of both genes, which are only 300 bp apart, were deleted. We conclude that the Leu1 and Leu2 genes are strong candidates as tumor suppressor gene(s) involved in B-CLL leukemogenesis.
authors.affiliation: Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Corcoran
authors.forename: O
authors.initials: O
authors.lastname: Rasool
authors.forename: G
authors.initials: G
authors.lastname: Ivanova
authors.forename: R
authors.initials: R
authors.lastname: Ibbotson
authors.forename: D
authors.initials: D
authors.lastname: Grandér
authors.forename: A
authors.initials: A
authors.lastname: Iyengar
authors.forename: A
authors.initials: A
authors.lastname: Baranova
authors.forename: V
authors.initials: V
authors.lastname: Kashuba
authors.forename: M
authors.initials: M
authors.lastname: Merup
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: A
authors.initials: A
authors.lastname: Gardiner
authors.forename: R
authors.initials: R
authors.lastname: Mullenbach
authors.forename: A
authors.initials: A
authors.lastname: Poltaraus
authors.forename: A L
authors.initials: AL
authors.lastname: Hultström
authors.forename: G
authors.initials: G
authors.lastname: Juliusson
authors.forename: R
authors.initials: R
authors.lastname: Chapman
authors.forename: M
authors.initials: M
authors.lastname: Tiller
authors.forename: F
authors.initials: F
authors.lastname: Cotter
authors.forename: G
authors.initials: G
authors.lastname: Gahrton
authors.forename: N
authors.initials: N
authors.lastname: Yankovsky
authors.forename: E
authors.initials: E
authors.lastname: Zabarovsky
authors.forename: S
authors.initials: S
authors.lastname: Einhorn
authors.forename: D
authors.initials: D
authors.lastname: Oscier
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D003001:Cloning, Molecular; D003360:Cosmids; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D017353:Gene Deletion; D015973:Gene Expression Regulation, Leukemic; D016147:Genes, Tumor Suppressor; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D014166:Transferases; D025521:Tumor Suppressor Proteins
chemical_list: C109421:DLEU1 lncRNA, human; C109420:DLEU2 lncRNA, human; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011506:Proteins; D062085:RNA, Long Noncoding; D025521:Tumor Suppressor Proteins; D014166:Transferases