■原位腺癌(AIS)和微创腺癌(MIA)被认为是肺腺癌(LUAD)的浸润前形式,5年无复发生存率为100%。我们研究了早期肿瘤发生中的基因组谱,并研究了侵袭性至浸润性腺癌(IAC)的突变特征以进行早期诊断。
■使用下一代测序从90例早期LUAD中国患者的689基因组中获得了分子信息。在病理亚型之间鉴定了基因特征,包括AIS/MIA(n=31)和IAC(n=59)。还从癌症基因组图谱(TCGA)获得突变和临床病理信息作为比较队列。
■TP53,RBM10,MUC1,CSMD,MED1,LRP1B,GLI1,MAP3K,在IAC中观察到RYR2,而在AIS/MIA组中观察到RYR2。AIS/MIA组的ERBB2、BRAF、GRIN2A,和RB1。队列中互斥基因(EGFR和KRAS)的突变率相当,突出了向侵入性LUAD的关键过渡。与TCGA队列相比,EGFR,KRAS,TP53和RBM10在两个队列中频繁突变。尽管队列之间的基因突变重叠有限,我们在侵袭性LUAD中观察到变异突变类型.此外,在中国队列(P=0.0053)和TCGA队列(P<0.01)中,AIS/MIA组的肿瘤突变负荷(TMB)值均显著低于IAC组.
■这些发现突出了在LUAD的早期阶段区分侵入前和侵入性LUAD的重要性,以及在临床实践中的病理和分子特征。揭示基因组肿瘤异质性和群体差异。
UNASSIGNED: Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are considered pre-invasive forms of lung adenocarcinoma (LUAD) with a 5-year recurrence-free survival of 100%. We investigated genomic profiles in early tumorigenesis and distinguished mutational features of preinvasive to invasive adenocarcinoma (IAC) for early diagnosis.
UNASSIGNED: Molecular information was obtained from a 689-gene panel in the 90 early-stage LUAD Chinese patients using next-generation sequencing. Gene signatures were identified between pathology subtypes, including AIS/MIA (n=31) and IAC (n=59) in this cohort. Mutational and clinicopathological information was also obtained from the Cancer Genome Atlas (TCGA) as a comparison cohort.
UNASSIGNED: A higher mutation frequency of TP53, RBM10, MUC1, CSMD, MED1, LRP1B, GLI1, MAP3K, and RYR2 was observed in the IAC than in the AIS/MIA group. The AIS/MIA group showed higher mutation frequencies of ERBB2, BRAF, GRIN2A, and RB1. Comparable mutation rates for mutually exclusive genes (EGFR and KRAS) across cohorts highlight the critical transition to invasive LUAD. Compared with the TCGA cohort, EGFR, KRAS, TP53, and RBM10 were frequently mutated in both cohorts. Despite limited gene mutation overlap between cohorts, we observed variant mutation types in invasive LUAD. Additionally, the tumor mutation burden (TMB) values were significantly lower in the AIS/MIA group than in the IAC group in both the Chinese cohort (P=0.0053) and TCGA cohort (P<0.01).
UNASSIGNED: These findings highlight the importance of distinguishing preinvasive from invasive LUAD in the early stages of LUAD and both pathology and molecular features in clinical practice, revealing genomic tumor heterogeneity and population differences.