Guo Sydney S, Wu Alan Y, Sawicki Mark P
Department of Surgery, West Los Angeles VA Medical Center and the UCLA School of Medicine, Los Angeles, CA 90073, USA.
World J Surg. 2002 Jul;26(7):843-7. doi: 10.1007/s00268-002-4062-4. Epub 2002 Apr 18.
Pancreatic endocrine tumors (PETs) may be sporadic or inherited in the multiple endocrine neoplasia type 1 (MEN-1) syndrome. The inherited form is caused by mutations of the MEN-1 gene, which functions as a tumor suppressor gene and maps to chromosome 11q13. These tumors tend to have a better prognosis than their sporadic counterparts, which often have mutations of the MEN-1 gene. Previous molecular analyses of sporadic PETs suggest a high frequency of loss of heterozygosity (LOH) at chromosome 1 as well as mutation of MEN-1. In this study we correlate abnormalities of MEN-1 and chromosome 1 LOH with the biological behavior of sporadic PETs. Loss of heterozygosity for markers at chromosome 11q13 and mutation of MEN-1 were equally frequent in tumors with or without liver metastases. Mutation of MEN-1 is more frequent in gastrinomas than in non-gastrinomas. Loss of heterozygosity for markers on chromosome 1 is more frequent in PETs with liver metastases. These results suggest a molecular tumor model in which there is a dichotomy in the development of benign and malignant PETs.
胰腺内分泌肿瘤（PETs）可能是散发性的，也可能是遗传性的，后者与多发性内分泌腺瘤1型（MEN-1）综合征相关。遗传性形式由MEN-1基因突变引起，该基因作为肿瘤抑制基因，定位于染色体11q13。这些肿瘤的预后往往比散发性肿瘤更好，后者通常存在MEN-1基因突变。先前对散发性PETs的分子分析表明，染色体1上杂合性缺失（LOH）的频率较高，同时也存在MEN-1突变。在本研究中，我们将MEN-1异常和染色体1 LOH与散发性PETs的生物学行为相关联。在有或无肝转移的肿瘤中，染色体11q13上标记物的杂合性缺失和MEN-1突变的频率相当。胃泌素瘤中MEN-1突变比非胃泌素瘤更常见。染色体1上标记物的杂合性缺失在有肝转移的PETs中更常见。这些结果提示了一种分子肿瘤模型，其中良性和恶性PETs的发展存在二分法。
