Analysis of a T-Cell Tumor-Specific Breakpoint Cluster at Human Chromosome 14q32

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 85; no. 23; pp. 9171 - 9175
• Main Authors: Mengle-Gaw, Laurel, Albertson, Donna G., Sherrington, Paul D., Rabbitts, Terence H.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.12.1988; National Acad Sciences
• Subjects: Base Sequence; Biological and medical sciences; Chromatin. Chromosome; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 14; Cloning, Molecular; Cytogenetics; DNA; DNA probes; Fundamental and applied biological sciences. Psychology; Gene Rearrangement, T-Lymphocyte; Genes; Genetic loci; Hematologic and hematopoietic diseases; Humans; In situ hybridization; Leukemia, T-Cell - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Multigene Family; Nucleic Acid Hybridization; T cell antigen receptors; T lymphocytes; Translocation, Genetic; Tumors; D14-Chromosome; Chromosomal aberration; Human; Immunoglobulins; Nervous system diseases; T cell receptor; Hemopathy; Carcinogenesis; Chronic lymphocytic leukemia; Gene; Abnormal «D14» chromosome; T-Lymphocyte; Gene rearrangement; Cytogenetics; Abnormal chromosome; Ataxia telangiectasia; Molecular biology; Chromosome inversion; Chromosome translocation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.85.23.9171

Cytogenetic abnormalities involving chromosome 14 band q32 are consistently observed in human T-cell tumors. Patients with ataxia-telangiectasia (AT) are especially prone to development of these tumors, which frequently carry either inversion inv(14)(q11;q32) or translocation t(14;14) (q11;q32) chromosomes. We have previously shown that the cytogenetic breakpoints of one t(14;14)(q11;q32) chromosome and two inv(14)(q11;q32) chromosomes in T-cell tumors from AT and non-AT patients join the T-cell receptor α chain locus, at chromosome band 14q11, with a region(s) at 14q32 centromeric of the immunoglobulin heavy chain variable region (VH) gene IGHV. We now show that these two inv(14) breakpoints are linked by 2.1 kb of germ-line 14q32 DNA and that the three breakpoints define, by in situ hybridization analysis, a single locus at chromosome band 14q32.1 located about 15-20 million base pairs on the centromeric side of the IGH locus. Sequence analysis of the 14q32.1 breakpoint regions indicates that abnormal recombination does not universally result from mistaken V-D-J joining (D = diversity region; J = joining region). Therefore, we invoke a tumor selection model to describe the role of the 14q32.1 locus in tumor development.