PMID- 8943844 OWN - NLM STAT- MEDLINE DCOM- 19961231 LR - 20240104 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 88 IP - 11 DP - 1996 Dec 1 TI - The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 gene. PG - 4110-7 AB - The t(9;14)(p13;q32) translocation is associated with approximately 50% of lymphoplasmacytoid lymphoma (LPL), a subtype of B-cell non-Hodgkin's lymphoma (NHL). We cloned the chromosomal breakpoint of der (14) from an LPL case (1052) and showed that it involved a junction between 9p13 and the switch micro region of the Ig heavy chain locus (IgH) on 14q32. Using a YAC contig spanning 1.5 megabase (Mb), we determined that the 9p13 breakpoint in one case (1052) mapped within a 270-kb restriction fragment containing two previously reported 9p breakpoints associated with a alpha-heavy chain disease case (MAL) and KI-1 positive diffuse large cell lymphoma (DLCL) cell line (KIS-1). The same fragment also contained the PAX-5 gene which encodes a B-cell specific transcription factor involved in the control of B-cell proliferation and differentiation. The breakpoints of KIS-1 and 1052 were mapped within the 5' noncoding region of PAX-5, while the 9p13 breakpoint of MAL mapped 230 to 270 kb upstream to PAX-5. In all three cases, the translocation caused the juxtaposition of the PAX-5 gene to the IgH locus in the opposite direction of transcription. When compared with six other DLCL cell lines lacking t(9;14)(p13;q32), the KIS-1 cell line showed an 11-fold overexpression of PAX-5 mRNA and a significantly reduced expression of the p53 gene, which is normally regulated by PAX-5. Moreover, metaphase and interphase fluorescence in situ hybridization (FISH) analysis using a YAC clone spanning 1 Mb including the PAX-5 as a probe identified chromosomal translocations in 5 of 7 cases carrying 9p13 translocations. These findings suggest that the PAX-5 gene is the target of the t(9;14) in LPL whereby its expression may be deregulated by juxtaposition to IgH regulatory elements, thus contributing to lymphomagenesis. FAU - Iida, S AU - Iida S AD - Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. FAU - Rao, P H AU - Rao PH FAU - Nallasivam, P AU - Nallasivam P FAU - Hibshoosh, H AU - Hibshoosh H FAU - Butler, M AU - Butler M FAU - Louie, D C AU - Louie DC FAU - Dyomin, V AU - Dyomin V FAU - Ohno, H AU - Ohno H FAU - Chaganti, R S AU - Chaganti RS FAU - Dalla-Favera, R AU - Dalla-Favera R LA - eng SI - GENBANK/U62539 GR - CA-34775/CA/NCI NIH HHS/United States GR - CA-44029/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (DNA, Neoplasm) RN - 0 (DNA-Binding Proteins) RN - 0 (Neoplasm Proteins) RN - 0 (Nuclear Proteins) RN - 0 (PAX5 Transcription Factor) RN - 0 (PAX5 protein, human) RN - 0 (Transcription Factors) SB - IM MH - Aged MH - Amino Acid Sequence MH - Base Sequence MH - Cell Transformation, Neoplastic/genetics MH - Chromosomes, Human, Pair 14/genetics/*ultrastructure MH - Chromosomes, Human, Pair 9/genetics/*ultrastructure MH - Cloning, Molecular MH - DNA, Neoplasm/genetics MH - DNA-Binding Proteins/*genetics/physiology MH - Exons/genetics MH - Female MH - Humans MH - In Situ Hybridization, Fluorescence MH - Leukemia, Lymphocytic, Chronic, B-Cell/*genetics/pathology MH - Molecular Sequence Data MH - Neoplasm Proteins/*genetics/physiology MH - Nuclear Proteins/*genetics/physiology MH - PAX5 Transcription Factor MH - *Transcription Factors MH - *Translocation, Genetic EDAT- 1996/12/01 00:00 MHDA- 1996/12/01 00:01 CRDT- 1996/12/01 00:00 PHST- 1996/12/01 00:00 [pubmed] PHST- 1996/12/01 00:01 [medline] PHST- 1996/12/01 00:00 [entrez] AID - S0006-4971(20)61153-3 [pii] PST - ppublish SO - Blood. 1996 Dec 1;88(11):4110-7.