Journal Article

A methylthioadenosine phosphorylase (MTAP) fusion transcript identifies a new gene on chromosome 9p21 that is frequently deleted in cancer

Rosenbach, Michael D, Schmid, Mathias, Friedman, Henry, Carson, Dennis A, Sen, Malini, Carrera, Carlos J

2000

Overview

Homozygous deletions of human chromosome 9p21 occur frequently in malignant cell lines, and are also common in primary gliomas, lung cancers, and leukemias. Moving from the centromere to the telomere, this complex region encodes the tumor suppressor genes p15INK4B (CDKN2B), p14ARF, p16INK4A (CDKN2A), and the housekeeping gene methylthioadenosine phosphorylase (MTAP). However, not all chromosome 9p21 deletions in tumors include these tumor suppressor genes. Here we describe the partial sequence and the exact localization of a new gene on chromosome 9p21 centromeric of p15INK4B, that formed an in frame fusion transcript with MTAP in a glioma xenograft, and that is homozygously deleted in various malignant cell lines. Northern blot revealed corresponding 1.5 kb transcript in non-deleted cell lines as well as in normal lymphocytes. Using a RNA master blot membrane including 50 different tissues, we could show that this new transcript is expressed in all tissues of the adult but not or only at very low levels in most of the fetal tissues tested. The expression pattern is similar to that of p16INK4A. The localization as well as the deletion pattern makes this transcript a candidate for a new tumor suppressor gene.

• Publisher: Nature Publishing,Nature Publishing Group
• Subject: 5'-Methylthioadenosine phosphorylase / Adult / Amino Acid Sequence / Animals / Base Sequence / Biological and medical sciences / Blotting, Northern / Blotting, Western / Brain tumors / Cancer / Carcinoma, Non-Small-Cell Lung - genetics / Carrier Proteins - genetics / Cell Cycle Proteins / Cell physiology / Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes / Child / Chromosome 9 / Chromosome Breakage / Chromosome Mapping / Chromosomes / Chromosomes, Human, Pair 9 / Cloning, Molecular / Cosmids - genetics / Cyclin-Dependent Kinase Inhibitor p15 / Cyclin-Dependent Kinase Inhibitor p16 / Exons / Fetuses / Fundamental and applied biological sciences. Psychology / Gene Deletion / Gene mutations / Genes / Genetic aspects / Glioma / Glioma - genetics / Health aspects / Humans / INK4a protein / Leukemia / Localization / Lung cancer / Lung Neoplasms - genetics / Lymphocytes / methylthioadenosine phosphorylase / Mice / Mice, Nude / Molecular and cellular biology / Molecular Sequence Data / Oncogene Proteins, Fusion - biosynthesis / Oncogene Proteins, Fusion - genetics / Oncogene Proteins, Fusion - isolation & purification / p14ARF gene / p15INK4B gene / p16 Protein / p16INK4A gene / Phosphorylase / Phosphorylases / Physiological aspects / Purine-Nucleoside Phosphorylase - biosynthesis / Purine-Nucleoside Phosphorylase - genetics / Purine-Nucleoside Phosphorylase - isolation & purification / Reverse Transcriptase Polymerase Chain Reaction / RNA, Messenger - biosynthesis / RNA, Messenger - genetics / Telomeres / Transcription / Transplantation, Heterologous / Tumor suppressor genes / Tumor Suppressor Proteins / Tumors / Xenografts