Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The familial occurrence of gliomas, in the absence of well-defined neurological tumor syndromes such as the neurofibromatoses, is uncommon. We present a family of ten children in which the four eldest suffered from gliomas. Three of these siblings had histologically verified glioblastoma multiforme, and one patient also had an intestinal non-Hodgkin's lymphoma, but there were no stigmata or family history of a neurological tumor syndrome. Cytogenetic studies of the proband revealed a normal karyotype. Molecular genetic analysis of the proband's glioblastoma revealed two mutations in the p53 tumor suppressor gene, but these were not present in the germline DNA, mutations were not detected in the MTS1 gene in the tumors or in the germline DNA. These findings suggest that a genetic factor may be responsible for the clustering of glial tumors in this family, but it is unlikely that the genetic alteration is mutation of the p53 gene. The data are discussed in light of the literature on familial brain tumors.
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PMID:Glioblastoma multiforme in four siblings: a cytogenetic and molecular genetic study. 759 55

The cyclin-dependent kinase 4-inhibitor (CDK41; p16; or MTS1) gene has been proposed as a candidate for a tumor-suppressor gene located in chromosome 9p21, a frequently deleted region in a wide spectrum of human cancers, including leukemias. Recent studies disclosed that it was frequently deleted or mutated in a variety of primary human cancers, including acute lymphoblastic leukemia. The purpose of this study is to figure out the precise manners and frequencies of p16 gene inactivation in diverse hematopoietic tumor types and thus to clarify its significance in development of human hematopoietic malignancies. A total of 410 tumor specimens from patients with primary hematopoietic malignancies were examined for deletions of the p16 gene as well as the neighboring p15 gene and the nearby interferon alpha gene by Southern blot analysis. Tumor-specific mutations or small deletions of the p16 gene were also studied in 74 patients using single-strand conformation polymorphism analysis and direct sequencing. Loss of the p16 gene was most frequently observed among the three genes examined and was found in 59 of the 410 patients: 2 of 134 with acute myelocytic leukemia, 41 of 105 with acute lymphocytic leukemia, 2 of 15 with chronic lymphocytic leukemia, 5 of 14 with adult T-cell leukemia, 4 of 33 with non-Hodgkin's lymphoma, 3 of 8 with mixed-lineage leukemia, and 2 of 61 with chronic myelocytic leukemia. In 16 of the 59 patients, the p16 deletions occurred due to rearrangements within the small region between the p15 exon 2 and the p16 exon 2. Tumor-specific mutations or small deletions of the p16 gene were not detected in the 74 patients examined, including 12 of 14 patients with hemizygous deletions of the gene. Loss of the p16 gene is frequent in and highly specific to lymphoid malignancies (54 of 183 [30%] in lymphoid tumor v2 of 219 [1%] in myeloid tumors; P < .0001). The deletion analyses strongly suggest that the p16 gene is a tumor-suppressor gene located in chromosome 9p21 that is involved in development of human lymphoid tumors. Gene deletions but not minute mutations should be the predominant mechanism of p16 gene inactivation in these types of tumors.
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PMID:Loss of the cyclin-dependent kinase 4-inhibitor (p16; MTS1) gene is frequent in and highly specific to lymphoid tumors in primary human hematopoietic malignancies. 763 63

The genes MTS1/p16 and MTS2/p15 located in 9p21 encoding cyclin-dependent kinase-4 inhibitors are homozygously deleted in a number of different tumour cell lines. By PCR analysis of 30 cell lines, including 10 acute lymphoblastic leukaemia (ALL) and 20 lymphoma cell lines, we found homozygous deletions of at least one locus in 11 (37%) cell lines. MTS1-specific sequences were deleted in 70% of ALL (reaching 86% in T-cell ALL) but in none of the non-Hodgkin's lymphoma (NHL) cell lines. MTS2-specific sequences were deleted in 40% of ALL and 17% of NHL cell lines. We observed a higher frequency of MTS1 deletions in ALL than in NHL (P < 0.001) and in T-cell neoplasms compared to B-cell neoplasms (67% v 6%; P = 0.001). In ALL-derived cell lines deletions of the MTS2 gene only occurred in cases with MTS1 deletions but in NHL only in cases without MTS1 deletions.
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PMID:Homozygous loss of the MTS1/p16 and MTS2/p15 genes in lymphoma and lymphoblastic leukaemia cell lines. 854 74

The p16 (CDKN2/MTS1/INK4a) malignant melanoma susceptibility gene was analyzed in 10 melanoma kindreds from southern Sweden using single-stranded conformation polymorphism analysis of all three exons and flanking intron regions followed by sequence analysis. A novel germline mutation, constituting an in-frame 3-bp duplication at nucleotide 332 in exon 2, was identified in two families (Lund M2 and M9). The mutation results in an insertion of Arg at codon 105, which interrupts the last of the four ankyrin repeats of the p16 protein, motifs which have been demonstrated as important in binding and inhibiting the activity of cyclin D-dependent kinases 4 and 6 in cell cycle G1 phase regulation. All five tested individuals of Lund M2 and M9 affected by melanoma were mutation carriers, as were five melanoma-free individuals. Other malignancies observed in gene carriers or obligate carriers included cervical, breast, and pancreatic carcinomas and a non-Hodgkin's lymphoma. Analysis of microsatellite markers adjacent to the p16 gene at chromosomal region 9p21 revealed that both families share a common haplotype, in keeping with a common ancestor.
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PMID:Novel germline p16 mutation in familial malignant melanoma in southern Sweden. 865 84