The activin type II receptorgene (ACTRII) is mutated in 58.1% of microsatellite-unstable (MSI-H) colorectal cancers and is a close relative of the TGFbeta-1 type II receptor, which is known to be involved in both MSI-H and non-MSI-H colorectal carcinogenesis. We therefore sought to determine whether ACTRII was involved in non-MSI-H colorectal cancers. We evaluated ACTRII inactivation by allelic deletion, loss of mRNA expression, or somatic mutation in 51 non-MSI-H colon cancers. Loss of heterozygosity (LOH) at the ACTRII locus (2q23.1) was found in 9 (17.6%) of 51 primary tumors. Loss of ACTRII mRNA expression was seen in one (14.3%) of the seven LOH-positive primary tumors from which total RNA was available. We also performed DNA sequencing analysis of tumors showing LOH. One LOH-positive primary tumor exhibited a novel germline missense sequence alteration (amino acid substitution, 117 Ile to Phe) that was not found in 23 additional normal individuals, implying that this alteration is not a frequent polymorphism. We conclude that ACTRII is probably involved in both non-MSI-H and MSI-H colorectal carcinogenesis, but more frequently in the latter subgroup.

中文翻译：

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人类结直肠肿瘤中 ACTRII 基因位点的杂合性缺失和突变分析。

激活素 II 型受体基因 (ACTRII) 在 58.1% 的微卫星不稳定 (MSI-H) 结直肠癌中发生突变，并且是 TGFbeta-1 II 型受体的近亲，后者已知参与 MSI-H 和非 MSI-H 结直肠癌发生。因此，我们试图确定 ACTRII 是否参与非 MSI-H 结直肠癌。我们评估了 51 例非 MSI-H 结肠癌中等位基因缺失、mRNA 表达缺失或体细胞突变导致的 ACTRII 失活。在 51 例原发性肿瘤中的 9 例 (17.6%) 中发现了 ACTRII 基因座 (2q23.1) 的杂合性缺失 (LOH)。在可获得总 RNA 的七个 LOH 阳性原发性肿瘤中，有一个 (14.3%) 观察到 ACTRII mRNA 表达缺失。我们还对显示 LOH 的肿瘤进行了 DNA 测序分析。一个 LOH 阳性原发性肿瘤表现出一种新的种系错义序列改变（氨基酸取代，117 Ile 到 Phe），而在另外 23 个正常个体中未发现这种改变，这意味着这种改变不是一种常见的多态性。我们得出结论，ACTRII 可能参与非 MSI-H 和 MSI-H 结直肠癌发生，但在后者亚组中更常见。