Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland, USA.
Hum Mutat. 2012 Jan;33(1):100-3. doi: 10.1002/humu.21633. Epub 2011 Nov 23.
Mutations in the chromatin remodeling gene ARID1A have recently been identified in the majority of ovarian clear cell carcinomas (OCCCs). To determine the prevalence of mutations in other tumor types, we evaluated 759 malignant neoplasms including those of the pancreas, breast, colon, stomach, lung, prostate, brain, and blood (leukemias). We identified truncating mutations in 6% of the neoplasms studied; nontruncating somatic mutations were identified in an additional 0.4% of neoplasms. Mutations were most commonly found in gastrointestinal samples with 12 of 119 (10%) colorectal and 10 of 100 (10%) gastric neoplasms, respectively, harboring changes. More than half of the mutated colorectal and gastric cancers displayed microsatellite instability (MSI) and the mutations in these tumors were out-of-frame insertions or deletions at mononucleotide repeats. Mutations were also identified in 2-8% of tumors of the pancreas, breast, brain (medulloblastomas), prostate, and lung, and none of these tumors displayed MSI. These findings suggest that the aberrant chromatin remodeling consequent to ARID1A inactivation contributes to a variety of different types of neoplasms.
染色质重塑基因 ARID1A 的突变最近在大多数卵巢透明细胞癌（OCCC）中被发现。为了确定其他肿瘤类型中突变的普遍性，我们评估了包括胰腺、乳腺、结肠、胃、肺、前列腺、脑和血液（白血病）在内的 759 种恶性肿瘤。我们在研究的肿瘤中发现了 6%的截断突变；另外还有 0.4%的肿瘤存在非截断性体细胞突变。突变最常见于胃肠道样本，分别有 119 个结直肠肿瘤中的 12 个（10%）和 100 个胃肿瘤中的 10 个（10%）发生了改变。超过一半的突变结直肠和胃癌显示出微卫星不稳定性（MSI），并且这些肿瘤中的突变是单核苷酸重复的移码插入或缺失。在胰腺、乳腺、脑（髓母细胞瘤）、前列腺和肺的肿瘤中也发现了突变，这些肿瘤均未显示出 MSI。这些发现表明，ARID1A 失活导致的异常染色质重塑可能与多种不同类型的肿瘤有关。
