Involvement of CDKN2 (p16INK4A/MTS1) and p15INK4B/MTS2 in human leukemias and lymphomas.
CDKN2 (p16INK4A/MTS1) and p15INK4B/MTS2 have been shown recently to be potent inhibitors of the cyclin D/cyclin-dependent kinase 4 complex. Both genes are candidates for the putative tumor suppressor gene located at chromosome 9p21. We examined a series of 14 hematopoietic cell lines and 117 primary lymphoid tumors for deletion and mutation of these genes. The primary tumors included 65 T-cell malignancies and 52 B-cell malignancies. The cell line study revealed 4 of 4 T-ALL lines to have homozygous deletions of CDKN2. Two of the 4 lines also showed homozygous deletions of MTS2, while the remaining 2 lines retained both MTS2 alleles. In the primary tumors, homozygous deletions of both CDKN2 and MTS2 were found in 35% of the T-ALL/lymphoblastic lymphoma (8 of 23). Homozygous deletions of both genes also occurred in 1 of 3 precursor B-ALLs. PCR-single strand conformational polymorphism analysis of CDKN2 exons 2 and 3 and MTS2 exon 2 failed to demonstrate mutations in either CDKN2 or MTS2 in any of the T- or B-cell malignancies, with two possible exceptions. These results are consistent with a role for CDKN2 and/or MTS2 in the pathogenesis of some lymphoid leukemia/lymphomas, particularly in T-ALL/lymphoblastic lymphoma.
Otsuki
T
T
Hematopathology Section, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Clark
H M
HM
Wellmann
A
A
Jaffe
E S
ES
Raffeld
M
M
D001483:Base Sequence; D015139:Blotting, Southern; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics; D016399:Lymphoma, T-Cell / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm