Lung cancer in the young is a rare entity of great interest due to the high frequency of targetable mutations. In this study, we explored the genomic landscape of non-small cell lung cancer (NSCLC) in young patients and compared it with genetic alterations in older patients.

Comparative study of the genomic profile of NSCLC young (≤40 years old) vs older patients (>40 years old) from Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru. Archival paraffin-embedded tumor samples were profiled with FoundationOne CDx assay to identify short variants alterations (insertions and deletions), copy number variations (CNV), tumor mutational burden and microsatellite instability in 324 driver genes and rearrangements in 28 commonly rearranged genes. A targetable alteration was defined as any alteration in a driver oncogene for which an FDA approved therapy existed at the time of study enrollment.

Overall, 62 tumors were profiled, 32 from young and 30 from older patients. All clinicopathological features (smoking status, clinical stage, and histology) were similar between groups, except for gender (65.6% of females in the younger group vs 40% in the older group, P=0.043). At least one actionable mutation was present in 84.4% and 83.3% in younger and older patients, respectively. Alteration rates in the main genes were: BRAF, 3.1%(n=1) vs 0%; EGFR, 46.9% (n=15) vs 43.3% (n=13); ERBB2, 12.5% (n=4) vs 16.7% (n=5); KRAS, 15.6% (n=5) vs 16.7% (n=5); ALK, 6.3% (n=2) vs 3.3% (n=1); RET, 0.0% vs 3.3% (n=1); ROS1, 3.1% (n=1) vs 3.3% (n=1); NTRK1, 0.0% vs 3.3% (n=1) and MET, 3.1% (n=1) vs 13.3% (n=4). Mean TMB was 4.04 Mut/Mb (SD ± 3.98) for young vs 8.06 Mut/Mb (SD ± 9.84) for older patients (P=0.016). There were not significant differences in CNV, frequency of gene rearrangements, or microsatellites instability.

NSCLC in the young in our cohort was characterized by a high frequency of actionable genetic aberrations and a low TMB, which was also true for our older patients. The enrichment of actionable mutations in young patients described in other reports might be attributed to differences in the etiology and clinicopathological characteristics between younger and older patients and therefore not be applicable to all populations.

由于可靶向突变的高频率，年轻人中的肺癌是一种罕见的引起极大兴趣的实体。在这项研究中，我们探索了年轻患者非小细胞肺癌 (NSCLC) 的基因组景观，并将其与老年患者的基因改变进行了比较。

来自秘鲁利马的 Instituto Nacional de Enfermedades Neoplásicas (INEN) 年轻（≤40 岁）与老年患者（>40 岁）的基因组图谱比较研究。使用 FoundationOne CDx 分析对档案石蜡包埋的肿瘤样本进行分析，以识别 324 个驱动基因中的短变体改变（插入和缺失）、拷贝数变异 (CNV)、肿瘤突变负荷和微卫星不稳定性以及 28 个常见重排基因中的重排。可靶向的改变被定义为在研究​​登记时存在 FDA 批准的治疗的驱动癌基因的任何改变。

总体而言，对 62 个肿瘤进行了分析，其中 32 个来自年轻患者，30 个来自老年患者。除性别外，各组之间的所有临床病理学特征（吸烟状态、临床分期和组织学）均相似（年轻组女性为 65.6%，老年组女性为 40%，P=0.043）。在年轻和老年患者中，分别有 84.4% 和 83.3% 存在至少一种可操作的突变。主要基因的改变率为：BRAF，3.1%(n=1) vs 0%；EGFR，46.9% (n=15) vs 43.3% (n=13)；ERBB2, 12.5% (n=4) vs 16.7% (n=5); KRAS，15.6% (n=5) vs 16.7% (n=5)；ALK，6.3% (n=2) vs 3.3% (n=1)；RET，0.0% 对 3.3% (n=1)；ROS1, 3.1% (n=1) vs 3.3% (n=1); NTRK1, 0.0% vs 3.3% (n=1) 和 MET, 3.1% (n=1) vs 13.3% (n=4)。年轻患者的平均 TMB 为 4.04 Mut/Mb (SD ± 3.98)，而老年患者的平均 TMB 为 8.06 Mut/Mb (SD ± 9.84) (P=0.016)。CNV 无显着差异，

我们队列中年轻人的 NSCLC 的特征是高频率的可操作基因畸变和低 TMB，这对于我们的老年患者也是如此。其他报告中描述的年轻患者中可操作突变的丰富可能归因于年轻患者和老年患者之间病因学和临床病理学特征的差异，因此不适用于所有人群。