BACKGROUND RAS/BRAF mutations of colorectal cancer (CRC) play a crucial role in carcinogenesis and cancer progression and need to be considered for the therapeutic strategy choice. We used next-generation-sequencing (NGS) technology to assess RAS/BRAF mutation differences between primary CRC and corresponding pulmonary metastases (PMs). METHODS We examined the mutation statuses of the KRAS 12/13/61/146, NRAS 12/13/61/146, and BRAF 600 codons in genomic DNA from fresh-frozen or formalin-fixed paraffin-embedded tissues derived from 34 primary lesions and 52 corresponding PMs from 36 patients with CRC. RESULTS We found RAS mutations in 76% (26/34) of primary CRC lesions and in 86% (31/36) of PMs. While 27% (7/26) of the primary CRC RAS mutations were heterogeneous, all the RAS mutations in PMs were homogeneous. Of the mutations in PMs, 71% (22/31) were KRAS G>A transitions, of which 82% (18/22) were KRAS G12D or G13D. The RAS mutation discordance between primary tumors and PMs was 12.1% (4/33). RAS mutations with the same genotyping were detected in all synchronous and metachronous PMs from 9 patients. We found no BRAF mutations in either primary or pulmonary tissues. CONCLUSION Our NGS analysis suggests that RAS mutations of PM of patients with CRC are more common than initially thought. The presence of KRAS mutations in CRC specimens, especially G12D or G13D mutations, seems to promote PM formation.

中文翻译：

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RAS突变在大肠癌患者肺转移中的意义。

背景大肠癌（CRC）的RAS / BRAF突变在致癌和癌症进展中起着至关重要的作用，因此需要考虑选择治疗策略。我们使用了下一代测序（NGS）技术来评估原发性CRC与相应肺转移（PM）之间的RAS / BRAF突变差异。方法我们检查了来自34个原发灶的新鲜冷冻或福尔马林固定石蜡包埋组织的基因组DNA中KRAS 12/13/61/146，NRAS 12/13/61/146和BRAF 600密码子的突变状态以及来自36例CRC患者的52个相应的PM。结果我们发现76％（26/34）的原发性CRC病变和86％（31/36）的PMs发生了RAS突变。虽然27％（7/26）的主要CRC RAS突变是异质的，但PM中的所有RAS突变都是同质的。在PM的突变中，71％（22/31）是KRAS G> A转换，其中82％（18/22）是KRAS G12D或G13D。原发性肿瘤与PM之间的RAS突变不一致率为12.1％（4/33）。在9例患者的所有同步和异时PM中检测到具有相同基因型的RAS突变。我们在原发或肺组织中均未发现BRAF突变。结论我们的NGS分析表明，CRC患者PM的RAS突变比最初想象的更为普遍。CRC标本中存在KRAS突变，尤其是G12D或G13D突变，似乎促进了PM的形成。我们在原发或肺组织中均未发现BRAF突变。结论我们的NGS分析表明，CRC患者PM的RAS突变比最初想象的更为普遍。CRC标本中存在KRAS突变，尤其是G12D或G13D突变，似乎促进了PM的形成。我们在原发或肺组织中均未发现BRAF突变。结论我们的NGS分析表明，CRC患者PM的RAS突变比最初想象的更为普遍。CRC标本中存在KRAS突变，尤其是G12D或G13D突变，似乎促进了PM的形成。