PTEN GENE ALTERATIONS IN LYMPHOID NEOPLASMS

Recently, a novel phosphatase designated PTEN/MMAC1/TEP1 and located o n chromosome 10q23.3 has been implicated as a new tumor suppressor gen e in human cancer. Allelic loss and mutation of this gene has been rep orted in epithelial derived tumors, including breast cancer and prosta te cancer, and in glioblastoma multiforme. The present study was desig ned to evaluate the potential involvement of PTEN in the pathogenesis of lymphoid neoplasms. We analyzed 27 hematopoietic cell lines (repres enting a variety of lymphoid lineages), 65 primary lymphoid tumors (in cluding 24 lymphoblastic leukemia/lymphoma [LBL], 30 large B-cell lymp homa [LBCL], 7 Burkitt's lymphoma [BL], and 4 anaplastic large cell ly mphoma [ALCL]), and 25 nonmalignant lymph node controls. Gene deletion and gross rearrangement were evaluated using Southern blot analysis, and mutations were studied by polymerase chain reaction (PCR)single-st rand conformation polymorphism (SSCP) (PCR-SSCP) and sequencing. Six o f 27 cell lines (22.2%) and 3 of 65 primary lymphomas (4.6%) contained alterations of this gene. A large homozygous deletion spanning exons 2 through 5 was detected in one LBL cell line, and two insertions pote ntially resulting in premature termination, were detected in a second LBL cell line. Nonconservative nucleotide variations were found in two other cell lines (one LBCL and one BL) and in one primary case of LBC L. In addition, two other cell lines (one BL and one myeloma) and two primary lymphomas, both LBCL, contained small deletions within intron 7. These deletions mapped to a poly-T-rich tract just 5' to the intron 7/exon 8 spice site. Their significance is unclear, as they may repre sent polymorphisms. Overall, our results suggest that abnormalities of the PTEN gene can contribute to pathogenesis in a small percentage of malignant lymphomas. This is a US government work. There are no restr ictions on its use.