Comprehensive analysis of age‐related somatic mutation profiles in Chinese young lung adenocarcinoma patients

Abstract

Background Lung adenocarcinoma in young adults is a rare entity with the oncogenic genetic alterations associated being poorly understood. In the present study, the effect of genetic alterations in lung adenocarcinoma patients diagnosed in young patients is reported. Methods Twenty young lung adenocarcinoma patients (age years: median: 33.5, range: 24‐36) were enrolled in the current study and 24 patients who were at common age of the disease onset (age years: median: 61.5, range: 52‐79) were selected for comparison. Paraffin sections of lung adenocarcinoma were analyzed using the whole‐exome sequencing platform. Results Similar number of somatic mutations per tumor were found in the young patients and their older counterparts. Although no age‐related differences were detected in the numbers of lung adenocarcinoma patients harboring well‐known gene variants, mutations in FRG1 and KMT2C were associated with a younger age especially after correcting for tobacco smoking and sex (FRG1: P = 0.027, KMT2C: P = 0.046). Five genetic variants showed higher alteration frequencies in young patients compared to the unclassified East Asian population, suggesting these mutations as disease‐related hereditary germline variants. Conclusions These results suggest different characteristics of lung adenocarcinoma between the young and the patients at common age of onset. Young patients with lung adenocarcinoma have a distinctly unique prevalence of oncogenic genetic alterations.

Targeted next-generation sequencing for cancer-associated gene mutation and copy number detection in 206 patients with non–small-cell lung cancer

“…In contrast to the widely reported high-frequency mutated genes mentioned above, CREBBP (23.1%), KMT2C (16.9%), MUC2 (16.6%), DNMT3A (15.5%), LRP1B (15.5%), MUC4 (15.5%), and CDC27 (15.2%) are currently reported less in the Chinese population, although mutations in DNMT3A and KMT2C have been identified in some studies [20,[33][34][35]. Our results suggest some aspects of the mutational characteristics of these genes in Chinese NSCLC, suggesting functions of these genes in the etiology and treatment of NSCLC.…”

Genomic profiling in non-small-cell lung cancer in young patients. A systematic review

“…Yang et al. 20 reported in 20 patients with LUAD and ≤36 years a similar number of somatic mutations per tumor than their older counterparts. Mutations in FRG1 and KMT2C were associated with a younger age especially after correcting for tobacco smoking and sex.…”

“… 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 Fourteen were reports from national databases. Our final selection for genomic profiling in AYA with lung cancer included 23 studies 4 , 7 , 8 , 9 , 11 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 40 , 41 , 43 , 44 ( Table 1 ).

Figure 1 PRISMA flow diagram of the literature search.

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“…One of the three studies that found significant differences in favor of young patients was the one carried out with a Caucasian population. 20 Interestingly, the specific EGFR mutation may vary between young and old patients. At least three studies showed that EGFR Del19 is significantly more prevalent among young patients and L858R is more prevalent among older patients.…”

Development and validation of a 4-gene combination for the prognostication in lung adenocarcinoma patients

“…Approximately, 85% of patients are non-small cell lung cancer, of which lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the most common subtypes. According to the epidemiological surveys in recent years, the incidence of LUAD has exceeded that of LUSC in both smokers and non-smokers in many countries, accounting for almost a half of all lung cancers; Even worse, in some countries, the incidence of LUAD in women is multiplying, and it also becomes the most common pathological type of lung cancer in young people [2,3]. Worst of all, LUAD is a kind of non-small cell lung…”