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IR@PKUHSC  > 北京大学临床肿瘤学院  > 病因研究室  > 期刊论文
学科主题: 临床医学
题名:
Clinical Implications of Microsatellite Instability and MLH1 Gene Inactivation in Sporadic Insulinomas
作者: Mei, Mei1; Deng, Dajun5; Liu, Tong-Hua2; Sang, Xin-Ting3; Lu, Xin3; Xiang, Hong-Ding4; Zhou, Jing5; Wu, HaiYan1; Yang, YingMai1; Chen, Jie2; Lu, Chong-Mei1; Chen, Yuan-Jia1,4
刊名: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
发表日期: 2009-09-01
DOI: 10.1210/jc.2009-0173
卷: 94, 期:9, 页:3448-3457
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Endocrinology & Metabolism
研究领域[WOS]: Endocrinology & Metabolism
关键词[WOS]: PANCREATIC ENDOCRINE NEOPLASMS ; NONPOLYPOSIS COLORECTAL-CANCER ; GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS ; PERFORMANCE LIQUID-CHROMATOGRAPHY ; MISMATCH REPAIR GENE ; PROMOTER METHYLATION ; MUTATION ANALYSIS ; CHROMOSOME 1Q ; COLON-CANCER ; HMLH1
英文摘要:

Context: The molecular pathogenesis of sporadic insulinomas is unknown. There is a lack of biomarker to distinguish benign and malignant form of insulinoma.

Objective: Our objective was to confirm the occurrence of microsatellite instability (MSI) in insulinomas, to identify alterations of mismatch repair (MMR) genes in the tumors, and to evaluate the possibility to distinguish benign and malignant insulinoma or to predict the clinical outcome of patients with these alterations.

Design and Patients: We detected MSI and inactivation of MLH1 gene in 55 sporadic insulinomas by PCR, immunohistochemical staining, allelic typing, analysis of promoter methylation, and exon mutations. Their correlations with clinicopathological characteristics were analyzed with univariate and multivariate statistic analysis.

Results: A high rate of MSI (MSI-H) was found in 33% of sporadic insulinomas. Reduced expression of mutL homolog 1 (MLH1) protein was observed in 36% of insulinomas and correlated with MSI-H (P = 0.008). Promoter methylation and loss of heterozygosity of MLH1 gene was found in 31 and 49% of insulinomas, respectively. Reduced expression of MLH1 and MSI-H were significantly associated with both tumor malignancy (P = 0.033 and P = 4.8 x 10(-6), respectively) and incurable disease (P = 0.006 and P = 0.001, respectively).

Conclusion: High frequency of MSI occurred in sporadic insulinomas. The silencing of MLH1 gene may partially contribute to the MSI-H in the tumors. Assessing MSI-Handexpressions of MLH1 could be used to distinguish benign and malignant insulinomas and to predict the outcome of patients. (J Clin Endocrinol Metab 94: 3448-3457, 2009)

语种: 英语
所属项目编号: 30570694 ; 2005CB522403
项目资助者: National Natural Sciences Foundation of China ; National Basic Research Program of China
WOS记录号: WOS:000269584600042
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/49867
Appears in Collections:北京大学临床肿瘤学院_病因研究室_期刊论文

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作者单位: 1.Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Gastroenterol, Beijing 100730, Peoples R China
2.Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Pathol, Beijing 100730, Peoples R China
3.Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Surg, Beijing 100730, Peoples R China
4.Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Endocrinol,Minist Hlth,Key Lab Endocrinol, Beijing 100730, Peoples R China
5.Peking Univ, Sch Oncol, Dept Etiol, Minist Educ,Key Lab Carcinogenesis & Translat Res, Beijing 100730, Peoples R China
6.Beijing Canc Hosp Inst, Beijing 100730, Peoples R China

Recommended Citation:
Mei, Mei,Deng, Dajun,Liu, Tong-Hua,et al. Clinical Implications of Microsatellite Instability and MLH1 Gene Inactivation in Sporadic Insulinomas[J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,2009,94(9):3448-3457.
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