BMI-1 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas

Citation
S. Bea et al., BMI-1 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas, CANCER RES, 61(6), 2001, pp. 2409-2412
Citations number
20
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
00085472 → ACNP
Volume
61
Issue
6
Year of publication
2001
Pages
2409 - 2412
Database
ISI
SICI code
0008-5472(20010315)61:6<2409:BGAAOI>2.0.ZU;2-6
Abstract
The BMI-1 gene Is a putative oncogene belonging to the Polycomb group famil y that cooperates with c-myc in the generation of mouse lymphomas and seems to participate in cell cycle regulation and senescence by acting as a tran scriptional repressor of the INK4a/ARF locus. The BIMI-1 gene has been loca ted on chromosome 10p13, a region involved in chromosomal translocations in infant leukemias, and amplified in occasional non-Hodgkin's lymphomas (NHL s) and solid tumors, To determine the possible alterations of this gene in human malignancies, we have examined 160 lymphoproliferative disorders, 13 myeloid leukemias, and 89 carcinomas by Southern blot analysis and detected BIMI-1 gene amplification (3- to 7-fold) in 4 of 36 (11%) mantle cell lymp homas (MCLs) with no alterations in the INK4a/ARF locus. BMI-1 and p16(INK4 a) mRNA and protein expression were also studied by real-time quantitative reverse transcription-PCR and Western blot, respectively, in a subset of NH Ls, BMI-1 expression was significantly higher in chronic lymphocytic leukem ia and MCL than in follicular lymphoma and large B cell lymphoma. The four tumors with gene amplification showed significantly higher mRNA levels than other MCLs and NHLs with the BMI-I gene in germline configuration. Five ad ditional MCLs also showed very high mRNA levels without gene amplification. A good correlation between BMI-1 mRNA levels and protein expression was ob served in all types of lymphomas, No relationship was detected between BMI- 1 and p16(INK4a) mRNA levels. These findings suggest that BMI-1 gene altera tions in human neoplasms are uncommon, but they may contribute to the patho genesis in a subset of malignant lymphomas, particularly of mantle cell typ e.