PTEN gene alterations in lymphoid neoplasms
PTEN gene alterations in lymphoid neoplasms
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DOI：
10.1182/blood.v92.9.3410.421a06_3410_3415
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发表时间：
1998-11-01
期刊：
影响因子：
20.3
通讯作者：
Raffeld, M
中科院分区：
文献类型：
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作者：
Sakai, A;Thieblemont, C;Raffeld, M
最近，一种位于染色体10q23.3上的新型磷酸酶PTEN/MMAC1/TEP1被认为是一种新的肿瘤抑制基因。该基因的等位基因丢失和突变已在上皮源性肿瘤中报道，包括乳腺癌和前列腺癌，以及多形性胶质母细胞瘤。本研究旨在评估PTEN在淋巴样肿瘤发病机制中的潜在参与。我们分析了27个造血细胞系（代表多种淋巴系）、65个原发性淋巴样肿瘤（包括24个淋巴母细胞白血病/淋巴瘤[LBL]、30个大b细胞淋巴瘤[LBCL]、7个伯基特淋巴瘤[BL]和4个间变性大细胞淋巴瘤[ALCL]）和25个非恶性淋巴结对照。采用Southern blot法分析基因缺失和重排，采用聚合酶链反应（PCR）、单链构象多态性（SSCP） （PCR-SSCP）和测序法研究基因突变。27个细胞系中的6个（22.2%）和65个原发性淋巴瘤中的3个（4.6%）含有该基因的改变。在一个LBL细胞系中检测到跨越外显子2到5的大纯合缺失，在另一个LBL细胞系中检测到两个可能导致过早终止的插入。在另外两个细胞系（一个LBCL和一个BL）和一个原发性LBCL病例中发现了非保守性核苷酸变异。此外，另外两个细胞系（一个BL和一个骨髓瘤）和两个原发性淋巴瘤，都是LBCL，在内含子7中含有小的缺失。这些缺失映射到一个富含poly- t的通道，距离7号内含子/ 8号外显子香料位点仅5'。它们的意义尚不清楚，因为它们可能代表多态性。总的来说，我们的结果表明PTEN基因的异常可能导致一小部分恶性淋巴瘤的发病。这是美国政府的工作。它的使用没有限制。
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. This is a US government work. There are no restrictions on its use.