Figure 3.

Intertumoral and intratumoral heterogeneity among different pathological subtypes. (A) Venn plots indicated intratumoral heterogeneity of somatic mutations within different pathological subtypes. (B) Venn plot of intertumoral heterogeneity of somatic mutations and tables showing mutated genes exclusively shared in the adenocarcinoma in the situ (AIS) and minimally invasive adenocarcinoma (MIA) group and the MIA or invasive adenocarcinoma (IAC) group, respectively. (C) Mutational spectra of different pathological subtypes. Box plot shows increasing discrimination of shared and unique mutations through linear pathological evolvement. (D) Visualized GISTIC analysis of copy number variants (CNVs) among three pathological subtypes and lung cancer–related genes are presented. Genes in red represent gain of copy number variants whereas genes in blue represent loss of copy number variants. AC092850.1, LOC100128002; ACAN, aggrecan gene; ALK, ALK receptor tyrosine kinase gene; ANKRD188; ankyrin repeat domain 1; ARVCF, ARVCF delta catenin family member gene; BAG1, BCL2 associated athanogene 1 gene; CENPB, centromere protein B gene; CHCD10, coiled-coil-helix-coiled-coil-helix domain containing 10 gene; CNTN1, contactin 1 gene; CSMD3, CUB and Sushi multiple domains 3 gene; CYP11A1, cytochrome P450 family 11 subfamily A member 1 gene; DNAH9, dynein axonemal heavy chain 9 gene; EMR2, adhesion G protein-coupled receptor E2 gene (this is the previous symbol; the current approved symbol is ADGRE2); ERBB2, erb-b2 receptor tyrosine kinase 2 gene; ERVW-1, endogenous retrovirus group W member 1, envelope gene; FAM230A, family with sequence similarity 230 member A gene; FGFR3, fibroblast growth factor receptor 3 gene; FGFR4, fibroblast growth factor receptor 3 gene; FGFRL1, fibroblast growth factor receptor like 1 gene; FMN2, formin 2 gene; FOLR3, folate receptor 3 gene; GOLGA6L2, golgin A6 family like 2 gene; GOLGA6L18, golgin A6 family like 10 gene (this is the previous symbol; the current approved symbol is GOLGA6L10); GOLGA8J, golgin A8 family member J gene; HDLBP, high density lipoprotein binding protein gene; IGHG1, immunoglobulin heavy chain constant gamma 1 (G1m marker) gene; IGSF3, immunoglobulin superfamily member 3 gene; KDM4E, lysine demethylase 4E gene; KIF21A, kinesin family member 21A gene; KIF25, kinesin family member 25 gene; MDC1, mediator of DNA damage checkpoint 1 gene; MDM4, MDM4 regulator of p53 gene; MED1, mediator complex subunit 1 gene; MTOR, mechanistic target of rapamycin kinase gene; MYCL1, v-myc avian myelocytomatosis viral oncogene lung carcinoma derived homolog gene; MYH1, myosin heavy chain 1 gene; MYH6, myosin heavy chain 6 gene; NOTCH1, notch 1 gene; OBP2B, odorant binding protein 2B gene; OR10G9, olfactory receptor family 10 subfamily G member 9 gene; OR2T33, olfactory receptor family 2 subfamily T member 33 gene; PARP4, poly(ADP-ribose) polymerase family member 4 gene; PCDH19, protocadherin 1 gene; PI4KA, phosphatidylinositol 4 kinase alpha gene; PRB2, proline rich protein BstN1 subfamily 1 gene; PRG4, proteoglycan 4 gene; PRR21, proline rich 21 gene; RIPK4, receptor interacting serine/threonine kinase 4 gene; SAMD9L, sterile alpha motif domain containing like 9 gene; SERPINI1, serpin family I member 1 gene; SOX1, SRY-box transcription factor 1 gene; SPRY4, sprouty RTK signaling antagonist 4 gene; STK11, serine/threonine kinase 11 gene; TERT, telomerase reverse transcriptase gene; TMEM259, transmembrane protein 259 gene; TP53, tumor protein p53 gene; TTF1, transcription termination factor 1 gene; TTN, titin gene; UGT2B11, UDP glucuronosyltransferase family 2 member B11 gene; VCX3B, variable change X-linked 3B gene; XIRP1, xin actin binding repeat containing 1 gene; ZFHX3, zinc finger homeobox 3 gene; ZP3, zona pellucida glycoprotein 3 gene.