Kimura M, Abe T, Sunamura M, Matsuno S, Horii A
Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Japan.
Genes Chromosomes Cancer. 1996 Oct;17(2):88-93. doi: 10.1002/(SICI)1098-2264(199610)17:2<88::AID-GCC3>3.0.CO;2-X.
As a first step toward understanding molecular mechanisms in human pancreatic carcinogenesis, we searched for the location of tumor suppressor genes by examining loss of heterozygosity (LOH) in 44 pancreatic cancer specimens. We used 46 microsatellite markers that spanned all of the autosomes. Frequent LOH was observed in six chromosomal regions: in chromosome arms lp (32%), 6q (37%), 9p (50%), 12q (30%), 17p (59%), and 18q (35%). Because chromosome arm 12q is a reported target for allelic loss in some other cancers, we focused on this region with 66 primary specimens and identified the minimal common region of allelic loss within a I-cM interval in 12q22-q23.l. Microsatellite instability (MI) was also examined in this study, and the incidence of MI(+) cases, in which MI of two or more microsatellite loci was detected, was 61% (27 of 44 informative cases). In pancreatic tumors with MI(+), mutations of the transforming growth factor beta receptor II (RII) gene were not detected.
作为了解人类胰腺癌发生分子机制的第一步，我们通过检测44例胰腺癌标本中的杂合性缺失（LOH）来寻找肿瘤抑制基因的位置。我们使用了覆盖所有常染色体的46个微卫星标记。在六个染色体区域观察到频繁的LOH：染色体臂1p（32%）、6q（37%）、9p（50%）、12q（30%）、17p（59%）和18q（35%）。由于染色体臂12q是其他一些癌症中报道的等位基因缺失靶点，我们用66例原发性标本聚焦于该区域，并在12q22 - q23.1的1厘摩区间内确定了等位基因缺失的最小共同区域。本研究还检测了微卫星不稳定性（MI），检测到两个或更多微卫星位点存在MI的MI（+）病例的发生率为61%（44例信息充分的病例中有27例）。在MI（+）的胰腺肿瘤中，未检测到转化生长因子β受体II（RII）基因的突变。
