Eubanks P J, Sawicki M P, Samara G J, Wan Y J, Gatti R A, Hurwitz M, Passaro E
Department of Surgery, Harbor-UCLA Medical Center, Torrance, California 90509, USA.
Am J Surg. 1997 Jun;173(6):518-20. doi: 10.1016/s0002-9610(97)00001-9.
Loss of heterozygosity (LOH) at chromosome 11q13 has been demonstrated in multiple endocrine neoplasia type I (MEN I) and sporadic parathyroid tumors, pituitary adenomas, and a few types of pancreatic endocrine tumors. Gastrinomas are the most common pancreatic endocrine tumor in MEN I. We hypothesized that all pancreatic endocrine tumors have LOH at 11q13, resulting in inactivation of the previously described tumor suppressor gene in this region.
We analyzed a sporadic gastrinoma, a MEN I-associated gastrinoma, and a nonfunctional pancreatic endocrine tumor from a patient with Von Hippel-Lindau (VHL) disease for LOH at seven loci at 11q13: D11S149, PYGM, D11S427, D11S546, SEA, D11S97, and D11S146.
We found LOH at 11q13 in all three tumors. The MEN I-associated gastrinoma we analyzed is the first tumor of this type to have LOH. This is also the first report of LOH at 11q13 in a pancreatic endocrine tumor from a patient with VHL. These findings suggest that the etiology of pancreatic endocrine tumor formation involves a common genetic pathway for sporadic, MEN I, and VHL tumors.
11q13染色体杂合性缺失（LOH）已在I型多发性内分泌肿瘤（MEN I）以及散发性甲状旁腺肿瘤、垂体腺瘤和少数类型的胰腺内分泌肿瘤中得到证实。胃泌素瘤是MEN I中最常见的胰腺内分泌肿瘤。我们推测所有胰腺内分泌肿瘤在11q13均存在LOH，导致该区域先前描述的肿瘤抑制基因失活。
我们分析了1例散发性胃泌素瘤、1例与MEN I相关的胃泌素瘤以及1例来自冯·希佩尔-林道（VHL）病患者的无功能胰腺内分泌肿瘤，检测其在11q13的7个位点（D11S149、PYGM、D11S427、D11S546、SEA、D11S97和D11S146）的LOH情况。
我们在所有这三种肿瘤中均发现了11q13的LOH。我们分析的与MEN I相关的胃泌素瘤是首例出现LOH的此类肿瘤。这也是关于VHL病患者胰腺内分泌肿瘤中11q13出现LOH的首例报道。这些发现提示胰腺内分泌肿瘤形成的病因涉及散发性、MEN I和VHL肿瘤的共同遗传途径。
