Ulivi Paola, Urbini Milena, Petracci Elisabetta, Canale Matteo, Dubini Alessandra, Bartolini Daniela, Calistri Daniele, Cravero Paola, Fonzi Eugenio, Martinelli Giovanni, Priano Ilaria, Andrikou Kalliopi, Bronte Giuseppe, Crinò Lucio, Delmonte Angelo
Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, Italy.
Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, Italy.
Cancers (Basel). 2022 May 10;14(10):2352. doi: 10.3390/cancers14102352.
Molecular characterization of advanced non-small-cell lung cancer (NSCLC) is mandatory before any treatment decision making. Next-generation sequencing (NGS) approaches represent the best strategy in this context. The turnaround time for NGS methodologies and the related costs are becoming more and more adaptable for their use in clinical practice. In our study, we analyzed a case series of young (under 65 years old) NSCLC patients with a wide NGS gene panel assay. The most frequent altered genes were TP53 (64.55%), followed by KRAS (44.1%), STK11 (26.9%), CDKN2A (21.5%), CDKN2B (14.0%), EGFR (16.1%), and RB1 (10.8%). Tumor mutational burden (TMB) was also evaluated. Considering the cut-off of 10 mut/Mb, 62 (68.9%) patients showed a TMB < 10 mut/Mb, whereas 28 (31.1%) showed a TMB ≥ 10 mut/Mb. STK11 and KRAS mutations were significantly associated with a higher TMB (p = 0.019 and p = 0.004, respectively). Conversely, EGFR and EML4-ALK alterations were more frequently found in tumors with low TMB (p = 0.019 and p < 0.001, respectively). We compared results obtained from this approach with those obtained from a single or few genes approach, observing perfect concordance of the results.
在做出任何治疗决策之前,对晚期非小细胞肺癌(NSCLC)进行分子特征分析是必不可少的。在这种情况下,下一代测序(NGS)方法是最佳策略。NGS方法的周转时间和相关成本在临床实践中的应用正变得越来越适用。在我们的研究中,我们分析了一系列年轻(65岁以下)NSCLC患者的广泛NGS基因panel检测结果。最常发生改变的基因是TP53(64.55%),其次是KRAS(44.1%)、STK11(26.9%)、CDKN2A(21.5%)、CDKN2B(14.0%)、EGFR(16.1%)和RB1(10.8%)。还评估了肿瘤突变负荷(TMB)。考虑到10个突变/Mb的临界值,62例(68.9%)患者的TMB<10个突变/Mb,而28例(31.1%)患者的TMB≥10个突变/Mb。STK11和KRAS突变与较高的TMB显著相关(分别为p = 0.019和p = 0.004)。相反,EGFR和EML4-ALK改变在TMB较低的肿瘤中更常见(分别为p = 0.019和p<0.001)。我们将这种方法获得的结果与单基因或少数基因方法获得的结果进行了比较,发现结果完全一致。