Irahara Natsumi, Baba Yoshifumi, Nosho Katsuhiko, Shima Kaori, Yan Liying, Dias-Santagata Dora, Iafrate Anthony John, Fuchs Charles S, Haigis Kevin M, Ogino Shuji
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Diagn Mol Pathol. 2010 Sep;19(3):157-63. doi: 10.1097/PDM.0b013e3181c93fd1.
Activating mutations in members of the RAS oncogene family (KRAS, HRAS, and NRAS) have been found in a variety of human malignancies, suggesting a dominant role in carcinogenesis. In colon cancers, KRAS mutations are common and clearly contribute to malignant progression. The frequency of NRAS mutations and their relationship with clinical, pathologic, and molecular features remains uncertain. We developed and validated a Pyroseqencing assay to detect NRAS mutations at codons 12, 13, and 61. Using a collection of 225 colorectal cancers from 2 prospective cohort studies, we examined the relationship between NRAS mutations, clinical outcome, and other molecular features, including mutation of KRAS, BRAF, and PIK3CA, microsatellite instability, and the CpG island methylator phenotype. Finally, we examined whether NRAS mutation was associated with patient survival or prognosis. NRAS mutations were detected in 5 (2.2%) of the 225 colorectal cancers and tended to occur in left-sided cancers arising in women, but did not seem to be associated with any of the molecular features that were examined.
在多种人类恶性肿瘤中均发现了RAS癌基因家族成员（KRAS、HRAS和NRAS）的激活突变，这表明其在致癌过程中起主要作用。在结肠癌中，KRAS突变很常见，且明显促进恶性进展。NRAS突变的频率及其与临床、病理和分子特征的关系仍不明确。我们开发并验证了一种焦磷酸测序法，用于检测NRAS基因第12、13和61密码子的突变。我们利用来自2项前瞻性队列研究的225例结直肠癌样本，研究了NRAS突变、临床结局与其他分子特征之间的关系，这些分子特征包括KRAS、BRAF和PIK3CA的突变、微卫星不稳定性以及CpG岛甲基化表型。最后，我们研究了NRAS突变是否与患者生存率或预后相关。在225例结直肠癌中，有5例（2.2%）检测到NRAS突变，且这些突变倾向于发生在女性左侧结肠癌中，但似乎与所检测的任何分子特征均无关联。
