Mismatch repair gene expression in malignant lymphoproliferative disorders of B-cell origin
Mismatch repair gene expression in malignant lymphoproliferative disorders of B-cell origin
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DOI：
10.1080/10428190290006215
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发表时间：
2002-02-01
影响因子：
2.6
通讯作者：
Papadimitriou, CS
中科院分区：
文献类型：
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作者：
Kotoula, V;Hytiroglou, P;Papadimitriou, CS
我们研究了错配修复（MMR）基因在31例b细胞源性恶性淋巴增生性疾病（25例淋巴瘤和6例浆细胞骨髓瘤）的淋巴组织标本和骨髓抽吸物中的表达。采用多重RT-PCR法评估hMSH2、hMLH1和hPMS1基因与P-actin基因的相对表达，P-actin基因被用作基因表达的内部控制。免疫组织化学进一步在蛋白水平上评价MSH2。将这些发现与没有恶性肿瘤证据的对照组淋巴组织标本（n = 6）进行比较。研究组31例患者中有10例（32%）出现MMR基因表达变化。6例浆细胞骨髓瘤中有2例的3种MMR基因转录物均低，而浆细胞骨髓瘤的骨髓被肿瘤细胞广泛浸润。hMSH2转录本在所有淋巴瘤病例中都存在，而hMLH1和hPMS1在一些大b细胞淋巴瘤（14例中分别有4例和5例）和囊胚型套细胞淋巴瘤（2例中有2例）中的表达明显低。7例b淋巴细胞白血病和2例中心细胞样套细胞淋巴瘤均未发现MMR基因畸变。这些发现表明hMSH2、hMLH1和hPMS1基因在不同类型b细胞淋巴增生性疾病中的表达率存在差异，提示MMR基因的表达可能与这些肿瘤的自然病程有关。本研究发现，与病程较轻的肿瘤相比，以侵袭性生物学行为为特征的淋巴瘤类型中MMR基因畸变的发生率更高。
We investigated mismatch repair (MMR) gene expression in 31 lymphoid tissue specimens and bone marrow aspirates with malignant lymphoproliferative disorders of B-cell origin (25 cases of lymphoma and six cases of plasma cell myeloma). A multiplex RT-PCR assay was employed to assess the relative expression of the hMSH2, hMLH1 and hPMS1 genes, as compared to P-actin, which was used as an internal control of gene expression. MSH2 was further evaluated at the protein level by immunohistochemistry. The findings were compared to those of a control group of lymphoid tissue specimens without evidence of malignancy (n = 6). Changes in MMR gene expression were observed in 10 out of 31 cases of the study group (32%). All three MMR gene transcripts were low in two out of six plasma cell myelomas, which had extensive bone marrow infiltration by neoplastic cells. The hMSH2 transcript was present in all cases of lymphoma, while the expression of hMLH1 and hPMS1 was significantly low in some large B-cell lymphomas (four and five out of 14 cases, respectively) and in mantle cell lymphomas of the blastoid type (two out of two cases). No MMR gene aberrations were found in seven cases of B-cell lymphocytic leukemia and two cases of mantle cell lymphoma of centrocyte-like type. These findings demonstrate that the expression rates of the hMSH2, hMLH1 and hPMS1 genes differ among various types of B-cell lymphoproliferative disorders, and suggest that MMR gene expression may be related to the natural history of these neoplasms. This study identified a higher incidence of MMR gene aberrations in lymphoma types characterized by aggressive biologic behavior, as compared to neoplasms with a more indolent course.