尽管治疗取得了进步，但转移性结直肠癌通常是致命的，需要基于分子发病机制的新方法来改善预后。一些结直肠癌的扩展 RAS 基因组（KRAS、NRAS、BRAF）基因中没有突变，代表一个特殊的子集，值得特殊的治疗考虑。使用 cBioportal 平台对来自公开基因组系列的结直肠癌的基因组图谱进行了询问。对没有 KRAS/NRAS 或 BRAF 突变的结直肠癌队列进行了评估，以检测由 PIK3CA 基因编码的激酶 PI3K 催化亚基 α 中是否存在突变。在不同的检查系列中，有 3.7% 至 7.6% 的结直肠癌出现这种情况。在所检查的不同系列中，所有四种基因均呈野生型配置（四重野生型）的患者占病例的 32.2% 至 39.9%。与四重野生型癌症相比，三重（KRAS/NRAS/BRAF）野生型/PIK3CA突变癌症的高TMB病例患病率较高，并且除TP53突变外，结直肠癌相关基因还存在其他突变。在三重野生型/PIK3CA 突变癌症中，编码表观遗传修饰剂和 DNA 损伤反应 (DDR) 的基因突变也更频繁。两组的预后相当。在没有KRAS/NRAS/BRAF突变的情况下，PIK3CA突变的结直肠癌经常出现表观遗传修饰因子和DDR反应基因的突变，这可能提供靶向机会。这些突变存在于四重野生型癌症的较小子集中。版权所有 © 2024，国际抗癌研究所（George J. Delinasios 博士），保留所有权利。

Despite therapeutic advancements, metastatic colorectal cancer is usually fatal, necessitating novel approaches based on the molecular pathogenesis to improve outcomes. Some colorectal cancers have no mutations in the extended RAS panel (KRAS, NRAS, BRAF) genes and represent a special subset, which deserves particular therapeutic considerations.The genomic landscape of colorectal cancers from publicly available genomic series was interrogated, using the cBioportal platform. Colorectal cancer cohorts with cancers devoid of KRAS/NRAS or BRAF mutations were evaluated for the presence of mutations in the catalytic sub-unit alpha of kinase PI3K, encoded by the gene PIK3CA.PIK3CA mutations in the absence of KRAS/NRAS/BRAF mutations were observed in 3.7% to 7.6% of colorectal cancers in the different series examined. Patients with all four genes in wildtype configuration (quadruple wild type) represented 32.2% to 39.9% of cases in the different series examined. Compared with quadruple wild type cancers, triple (KRAS/NRAS/BRAF) wild type/PIK3CA mutated cancers had a higher prevalence of high TMB cases and additional mutations in colorectal cancer associated genes except for mutations in TP53. Mutations in genes encoding for epigenetic modifiers and the DNA damage response (DDR) were also more frequent in triple wild type/PIK3CA mutated cancers. The prognosis of the two groups was comparable.Colorectal cancers with PIK3CA mutations in the absence of KRAS/NRAS/BRAF mutations have frequently mutations in epigenetic modifiers and DDR response genes, which may provide opportunities for targeting. These mutations are present in a smaller subset of quadruple wild type cancers.Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.