Somatic PTEN mutations are common and have driver function in some cancer types. However, in colorectal cancers (CRCs), somatic PTEN-inactivating mutations occur at a low frequency (~8–9%), and whether these mutations are actively selected and promote tumor aggressiveness has been controversial. Analysis of genomic data from ~53,000 CRCs indicates that hotspot mutation patterns in PTEN partially reflect DNA-dependent selection pressures, but also suggests a strong selection pressure based on protein function. In microsatellite stable (MSS) tumors, PTEN alterations co-occur with mutations activating BRAF or PI3K, or with TP53 deletions, but not in CRC with microsatellite instability (MSI). Unexpectedly, PTEN deletions are associated with poor survival in MSS CRC, whereas PTEN mutations are associated with improved survival in MSI CRC. These and other data suggest use of PTEN as a prognostic marker is valid in CRC, but such use must consider driver mutation landscape, tumor subtype, and category of PTEN alteration.

体细胞PTEN突变很常见，并且在某些癌症类型中具有驱动功能。然而，在结直肠癌（CRC）中，体细胞PTEN失活突变的发生频率较低（约 8-9%），并且这些突变是否被主动选择并促进肿瘤侵袭性一直存在争议。对约 53,000 个 CRC 的基因组数据的分析表明， PTEN中的热点突变模式部分反映了 DNA 依赖性选择压力，但也表明基于蛋白质功能的强大选择压力。在微卫星稳定 (MSS) 肿瘤中，PTEN改变与激活BRAF或PI3K的突变或TP53缺失同时发生，但在具有微卫星不稳定 (MSI) 的 CRC 中则不然。出乎意料的是，PTEN缺失与 MSS CRC 的生存率较低有关，而PTEN突变与 MSI CRC 的生存率提高有关。这些和其他数据表明，使用PTEN作为预后标志物在 CRC 中是有效的，但这种使用必须考虑驱动突变情况、肿瘤亚型和PTEN改变的类别。