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Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3410-3415
PTEN Gene Alterations in Lymphoid Neoplasms
Akira Sakai,
Catherine Thieblemont,
Axel Wellmann,
Elaine S. Jaffe, and
Mark Raffeld
From the Hematopathology Section, Laboratory of
Pathology, National Cancer Institute, National Institutes of Health,
Bethesda, MD.
Recently, a novel phosphatase designated PTEN/MMAC1/TEP1 and located
on chromosome 10q23.3 has been implicated as a new tumor suppressor
gene in human cancer. Allelic loss and mutation of this gene has been
reported in epithelial derived tumors, including breast cancer and
prostate cancer, and in glioblastoma multiforme. The present study was
designed to evaluate the potential involvement of PTEN in the
pathogenesis of lymphoid neoplasms. We analyzed 27 hematopoietic cell
lines (representing a variety of lymphoid lineages), 65 primary
lymphoid tumors (including 24 lymphoblastic leukemia/lymphoma [LBL],
30 large B-cell lymphoma [LBCL], 7 Burkitt's lymphoma [BL], and 4 anaplastic large cell lymphoma [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-strand conformation polymorphism (SSCP)
(PCR-SSCP) and sequencing. Six of 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 potentially 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 LBCL. 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 represent
polymorphisms. Overall, our results suggest that abnormalities of the
PTEN gene can contribute to pathogenesis in a small percentage of
malignant lymphomas.
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