Souza R F, Lei J, Yin J, Appel R, Zou T T, Zhou X, Wang S, Rhyu M G, Cymes K, Chan O, Park W S, Krasna M J, Greenwald B D, Cottrell J, Abraham J M, Simms L, Leggett B, Young J, Harpaz N, Meltzer S J
Department of Medicine, University of Maryland School of Medicine, Baltimore, USA.
Gastroenterology. 1997 Jan;112(1):40-5. doi: 10.1016/s0016-5085(97)70217-8.
BACKGROUND & AIMS: Numerous gastrointestinal tumors, notably sporadic and ulcerative colitis (UC)-associated colorectal carcinomas and dysplasias, gastric cancers, and esophageal carcinomas, manifest microsatellite instability. Recently, a transforming growth factor beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in colorectal carcinomas showing instability. One hundred thirty-eight human neoplasms (61 UC-associated, 35 gastric, 26 esophageal, and 16 sporadic colorectal) were evaluated for this TGF-beta 1RII mutation.
Whether instability was present at other chromosomal loci in these lesions was determined. In lesions manifesting or lacking instability, the TGF-beta 1RII coding region polydeoxyadenine (poly A) microsatellite tract was polymerase chain reaction amplified with 32P-labeled deoxycytidine triphosphate. Polymerase chain reaction products were electrophoresed on denaturing gels and exposed to radiographic film.
Three of 18 UC specimens with instability at other chromosomal loci (17%) showed TGF-beta 1RII poly A tract mutation, including 2 cancers and 1 dysplasia; moreover, 2% of UC specimens without instability (1 of 43) (1 cancer), 81% of unstable sporadic colorectal cancers (13 of 16), and none of the 61 stable or unstable gastric or esophageal cancers contained TGF-beta 1RII mutations.
Mutational inactivation of the poly A microsatellite tract within TGF-beta 1RII occurs early and in a subset of unstable UC neoplasms and commonly in sporadic colorectal cancers but may be rare in unstable gastric and esophageal tumors.
许多胃肠道肿瘤，尤其是散发性和溃疡性结肠炎（UC）相关的结直肠癌及发育异常、胃癌和食管癌，均表现出微卫星不稳定性。最近，在显示不稳定性的结直肠癌中描述了编码微卫星中的转化生长因子β1Ⅱ型受体（TGF-β1RII）突变。对138例人类肿瘤（61例UC相关、35例胃、26例食管和16例散发性结直肠癌）进行了该TGF-β1RII突变评估。
确定这些病变中其他染色体位点是否存在不稳定性。在表现出或缺乏不稳定性的病变中，用32P标记的三磷酸脱氧胞苷对TGF-β1RII编码区多聚脱氧腺嘌呤（poly A）微卫星序列进行聚合酶链反应扩增。聚合酶链反应产物在变性凝胶上进行电泳，并与放射自显影片曝光。
18例在其他染色体位点存在不稳定性的UC标本中有3例（17%）显示TGF-β1RII poly A序列突变，包括2例癌症和1例发育异常；此外，43例无不稳定性的UC标本中有1例（2%）（1例癌症），16例不稳定散发性结直肠癌中有13例（81%），61例稳定或不稳定的胃癌或食管癌均未检测到TGF-β1RII突变。
TGF-β1RII内的poly A微卫星序列的突变失活在不稳定的UC肿瘤亚组中早期发生，在散发性结直肠癌中常见，但在不稳定的胃和食管肿瘤中可能罕见。
