Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.
Department of Medical Genetics, National Taiwan University Hospital, Taipei.
Am J Clin Pathol. 2019 Oct 7;152(5):570-581. doi: 10.1093/ajcp/aqz077.
To propose an operating procedure for validation of discordant trunk driver mutations.
Concordance of trunk drivers was examined by next-generation sequencing in 15 patients with two to three metastatic lung cancers and 32 paired primary and metastatic lung cancers.
Tissue identity was confirmed by genotyping 17 single-nucleotide polymorphisms within the panel. All except three pairs showed concordant trunk drivers. Quality assessment conducted in three primary and metastatic pairs with discordant trunk drivers indicates metastasis from a synchronous or remote lung primary in two patients. Review of literature revealed high discordant rates of EGFR and KRAS mutations, especially when Sanger sequencing was applied to examine primary and lymph node metastatic tumors.
Trunk driver mutations are highly concordant in primary and metastatic tumors. Discordance of trunk drivers, once confirmed, may suggest a second primary cancer. Guidelines are recommended to establish standard operating procedures for validation of discordant trunk drivers.
提出一种用于验证不匹配的主干驱动突变的操作程序。
通过对 15 例有 2 至 3 处转移性肺癌和 32 对原发性和转移性肺癌的患者进行下一代测序，来检查主干驱动的一致性。
通过对面板内的 17 个单核苷酸多态性进行基因分型，证实了组织同一性。除了三对之外，所有配对均显示出一致的主干驱动。对三对有不匹配主干驱动的原发性和转移性配对进行质量评估表明，两名患者的转移来自同步或远处的肺原发灶。文献复习显示 EGFR 和 KRAS 突变的不匹配率很高，尤其是当应用 Sanger 测序来检查原发性和淋巴结转移性肿瘤时。
原发性和转移性肿瘤中的主干驱动突变高度一致。一旦确认主干驱动不匹配，可能提示为第二原发癌。建议制定指南，以建立验证不匹配主干驱动的标准操作程序。
