Nucleotide sequence, transcription map, and mutation analysis of the 13q14 chromosomal region deleted in B-cell chronic lymphocytic leukemia.

TitleNucleotide sequence, transcription map, and mutation analysis of the 13q14 chromosomal region deleted in B-cell chronic lymphocytic leukemia.
Publication TypeJournal Article
Year of Publication2001
AuthorsMigliazza A, Bosch F, Komatsu H, Cayanis E, Martinotti S, Toniato E, Guccione E, Qu X, Chien M, Murty VV, Gaidano G, Inghirami G, Zhang P, Fischer S, Kalachikov SM, Russo J, Edelman I, Efstratiadis A, Dalla-Favera R
Date Published2001 Apr 01
KeywordsAnimals, Base Sequence, Cell Transformation, Neoplastic, Chromosome Mapping, Chromosomes, Human, Pair 13, DNA Mutational Analysis, DNA, Complementary, DNA, Neoplasm, Expressed Sequence Tags, Gene Expression Regulation, Leukemic, Genes, Tumor Suppressor, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Mice, Molecular Sequence Data, Proteins, Pseudogenes, RNA, Messenger, RNA, Neoplasm, Sequence Deletion, Transcription, Genetic, Transferases, Tumor Suppressor Proteins

Deletions of the 13q14 chromosome region are associated with B-cell chronic lymphocytic leukemia (B-CLL) and several other types of cancer, suggesting the presence of a tumor suppressor gene. In previous studies the minimal region of deletion (MDR) was mapped to a less than 300-kilobase (kb) interval bordered by the markers 173a12-82 and 138G4/1.3R. For the identification of the putative tumor suppressor gene, the entire MDR (approximately 347 kb) has been sequenced, and transcribed regions have been identified by exon trapping, EST-based full-length complementary DNA cloning, database homology searches, and computer-assisted gene prediction analyses. The MDR contains 2 pseudogenes and 3 transcribed genes: CAR, encoding a putative RING-finger containing protein; 1B4/Leu2, generating noncoding transcripts; and EST70/Leu1, probably representing another noncoding gene (longest open reading frame of 78 codons). These genes have been sequenced in 20 B-CLL cases with 13q14 hemizygous deletion, and no mutations were found. Moreover, no somatic variants were found in the entire MDR analyzed for nucleotide substitutions by a combination of direct sequencing and fluorescence-assisted mismatch analysis in 5 B-CLL cases displaying 13q14-monoallelic deletion. The nondeleted allele of the CAR and EST70/Leu1 genes was expressed in B-CLL specimens, including those with monoallelic loss, whereas no expression of 1B4/Leu2 was detectable in B-CLL, regardless of the 13q14 status. These results indicate that allelic loss and mutation of a gene within the MDR is an unlikely pathogenetic mechanism for B-CLL. However, haplo-insufficiency of one of the identified genes may contribute to tumorigenesis. (Blood. 2001;97:2098-2104)

Alternate JournalBlood
PubMed ID11264177
Related Faculty: 
Giorgio Inghirami, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700