Clinicopathologic characteristics and genomic profiling among different subtypes of lung adenocarcinoma (LUAD). (A) Pathological and corresponding radiological images of three representative pathological subtypes. Red arrow indicates the annotation of the lesion. (B) Comprehensive visualized plot based on surgical specimens of patients with adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive carcinoma (IAC) lesions. Each column represents a single patient whose specimen was examined by multiregion sequencing. Top bar graph describes the mutation number in each patient. Key characteristics, including age, sex, smoking status, and radiological pattern, are presented as a heatmap below the bar graph. Mutation recurrent rate is illustrated by bar graph to the left. Selected genes that have been reported to be correlated with lung adenocarcinoma are shown in the middle heatmap. (C) Driver alterations of EGFR, erb-b2 receptor tyrosine kinase 2 gene (ERBB2), BRAF, and NRAS are specifically presented through a heatmap. (D) Dual bar graph of stage I lung adenocarcinomas, most of which are bronchioloalveolar carcinomas from four external cohorts, reveals both somatic nucleotides variants and copy number variants of several genes with the largest proportion and driver genes. ALK, ALK receptor tyrosine kinase; ALK, ALK receptor tyrosine kinase gene; APA, acinar predominant adenocarcinoma; ARMS, amplification refractory mutation system; CDKN2A, cyclin dependent kinase inhibitor 2A gene; CDKN2B, cyclin dependent kinase inhibitor 2B gene; CKS1B, CDC29 protein kinase regulatory subunit 1B; CNA, copy number alteration; CRIPAK, cysteine rich PAK1 inhibitor gene; CRNN, cornulin gene; DMD, dystrophin gene; DROSHA, drosha ribonuclease 3 gene; ERBB2, erb-b2 receptor tyrosine kinase 2 gene; ERBB4, erb-b2 receptor tyrosine kinase 24 gene; FLG, filaggrin gene; GOLPH3, golgi phosphoprotein 3 gene; ICE1, interactor of elongation complex ELL subunit 1 gene; IHC, immunohistochemistry; IL7R, interleukin 7 receptor gene; KEAP1, kelch like ECH associated protein 1 gene; LFR, intelectin 1 gene (approved symbol is now ITLN1); LPA, lepidic predominant adenocarcinoma; LRP1B, LDL receptor related protein 1B gene; MET, MET proto-oncogene, receptor tyrosine kinase; MET, MNNG HOS Transforming gene; mGGO, mixed ground glass opacity; MIA, MIA SH3 domain containing gene; MTAP, methylthioadenosine phosphorylase gene; MUC16, mucin 16, cell surface associated gene; NBPF6, NBPF member 6 gene; NOTCH2, notch 2 gene; pGGO, pure ground glass opacity; PRB1, proline rich protein BstN1 subfamily 1 (gene/pseudogene) gene; PRDM9, R/SET domain 9 gene; PTPRD, protein tyrosine phosphatase, receptor type D gene; RB1, retinoblastoma gene; RET, ret proto-oncogene gene; RICTOR, RPTOR independent companion of MTOR complex 2 gene; RYR2, ryanodine receptor 2 gene; SDHA, succinate dehydrogenase complex flavoprotein subunit A gene; SKP2, S-phase kinase associated protein 2 gene; SPTA1, spectrin alpha, erythrocytic 1 gene; STK11, serine/threonine kinase 11 gene; SYNE2, spectrin repeat containing nuclear envelope protein 1 gene; TERT, telomerase reverse transcriptase gene; TNR, tenascin R gene; TP53, tumor protein p53 gene; TTN, titin gene; TXNDC2, thioredoxin domain containing 2 gene; USH2A, usherin gene; ZFHX4, zinc finger homeobox 4 gene; ZNF536, zinc finger protein 536 gene.