基于杂合性缺失分析的I型多发性内分泌肿瘤（MEN1）基因定位

Localization of the multiple endocrine neoplasia type I (MEN1) gene based on tumor loss of heterozygosity analysis.

作者信息

Emmert-Buck M R, Lubensky I A, Dong Q, Manickam P, Guru S C, Kester M B, Olufemi S E, Agarwal S, Burns A L, Spiegel A M, Collins F S, Marx S J, Zhuang Z, Liotta L A, Chandrasekharappa S C, Debelenko L V

机构信息

Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA.

出版信息

Cancer Res. 1997 May 15;57(10):1855-8.

PMID:9157974

Abstract

Multiple endocrine neoplasia type I (MEN1) is an inherited syndrome that results in parathyroid, anterior pituitary, and pancreatic and duodenal endocrine tumors as well as foregut carcinoids in affected patients. The gene responsible for the disease has been linked to chromosome 11q13. We analyzed loss of heterozygosity (LOH) in 188 tumors from 81 patients in an attempt to further define the location of the MEN1 gene. Both tumors from MEN1 patients and corresponding sporadic tumors were analyzed. Tumor types included parathyroid, gastrinoma, pancreatic endocrine, pituitary, and lung carcinoid. Six tumors (three MEN1 and three sporadic tumors) were identified that provided important LOH boundaries. Four tumors (two parathyroid tumors, one gastrinoma, and one lung carcinoid tumor) showed allelic loss that placed the MEN1 gene distal to marker PYGM. Two tumors (one gastrinoma and one parathyroid tumor) showed an LOH boundary that placed the gene proximal to D11S449, one of which further moved the telomeric boundary to D11S4936. Taken together, the present data suggest that the MEN1 gene lies between PYGM and D11S4936, a region of approximately 300 kb on chromosome 11q13.

摘要

多发性内分泌腺瘤 1 型（MEN1）是一种遗传性综合征，可导致受影响患者发生甲状旁腺、垂体前叶、胰腺和十二指肠内分泌肿瘤以及前肠类癌。导致该疾病的基因已与 11q13 染色体相关联。我们分析了 81 例患者的 188 个肿瘤中的杂合性缺失（LOH），以进一步确定 MEN1 基因的位置。对 MEN1 患者的肿瘤和相应的散发性肿瘤均进行了分析。肿瘤类型包括甲状旁腺、胃泌素瘤、胰腺内分泌肿瘤、垂体肿瘤和肺癌类癌。鉴定出六个肿瘤（三个 MEN1 肿瘤和三个散发性肿瘤），它们提供了重要的 LOH 边界。四个肿瘤（两个甲状旁腺肿瘤、一个胃泌素瘤和一个肺癌类癌肿瘤）显示等位基因缺失，这将 MEN1 基因定位在标记 PYGM 的远端。两个肿瘤（一个胃泌素瘤和一个甲状旁腺肿瘤）显示出一个 LOH 边界，该边界将基因定位在 D11S449 的近端，其中一个进一步将端粒边界移至 D11S4936。综合来看，目前的数据表明 MEN1 基因位于 PYGM 和 D11S4936 之间，这是 11q13 染色体上大约 300 kb 的区域。