Multi-Omics Characterization and Origin Assessment of Bilateral Lung Adenoid Cystic Carcinoma: A Case Report

Figures & data

Table 1 Genetic Alterations in the Three Adenoid Cystic Carcinomas

Sample	Mutation Type	Gene	AAChange	Ref	Alt	InterVar Classification	Cosmic ID
LLL	Mutant	PIK3R1	c.201dup (p.I68Yfs*8)	–	T	Likely pathogenic
	Mutant	LYN	c.1079G>A (p.R360Q)	G	A	Uncertain significance
	Mutant	SPOP	c.361C>T (p.R121W)	G	A	Uncertain significance	COSM2698401
	Mutant	SETD2	c.4929C>G (p.N1643K)	G	C	Uncertain significance
	Mutant	FBXW7	c.1034C>T (p.T345I)	G	A	Uncertain significance	COSM6993417; COSM6993415; COSM6993414; COSM6993416; COSM6993412; COSM6993413
	CNV	MCL1
	MS		MSS
	TMB
RML	Mutant	PIK3R1	c.201dup (p.I68Yfs*8)	–	T	Likely pathogenic
	MS		MSS
	TMB
RLL	MS		MSS
	TMB
Blood	SNP	DPYD	c.1627A>G (p.I543V)	T	C	Benign	COSM3747121
	SNP	ERCC1	c.354T>C (p.N118=)	A	G	Benign
	SNP	ERCC2	c.2251A>C (p.K751Q)	T	G	Benign	COSM4132125
	SNP	NQO1	c.559C>T (p.P187S)	G	A	Uncertain significance	COSM148097
	SNP	TYMS 6bp	c.*450_*455delAAGTTA	TTAAAG	–	Benign
	SNP	UGT1A1	c.211G>A (p.G71R)	G	A	Uncertain significance	COSM4415617; COSM4415616
	SNP	GSTT1
	TMB

Notes: *COSMIC, the Catalogue of Somatic Mutations in Cancer; InterVar, a bioinformatics software tool for clinical interpretation of genetic variants by the ACMG/AMP 2015 guideline, defining variants into “Benign”, “Likely benign”, “Uncertain significance”, “Likely pathogenic” and “Pathogenic”, together with detailed evidence code.

Figure 1 Genetic alterations of the presented multiple ACC lesions.

Abbreviations: LLL, left lower lobe; RML, right middle lobe; RLL, right lower lobe.

Table 2 Overlapped Top 10 Upregulated GO Terms in the Three Malignant Tumours

Term	Description	P-value in RML	P-value in RLL	P-value in LLL	Overlap Enrichment
Biological Process
GO:006351	Transcription, DNA-templated	4.09114E-06	3.34546E-07	–	Unique in right lesions
GO:0006355	Regulation of transcription, DNA-templated	7.11726E-06	3.61249E-07	–	Unique in right lesions
GO:0002934	Desmosome organization	2.58612E-05	5.49273E-07	–	Unique in right lesions
GO:0030198	Extracellular matrix organization	–	9.67886E-06	4.76496E-06	Transitional
GO:0007155	Cell adhesion	1.77278E-05	9.73916E-06	–	Unique in right lesions
Molecular Function
GO:0003677	DNA binding	1.78152E-06	5.66698E-08	0.000783362	Common Enrichment
GO:0000166	Nucleotide binding	0.00058113	5.7697E-06	0.002607564	Common Enrichment
GO:0005515	Protein binding	1.16842E-09	3.0942E-10	7.03011E-05	Common Enrichment
GO:0003700	Transcription factor activity, sequence-specific DNA binding	6.32364E-06	1.68874E-05	4.56837E-06	Common Enrichment
GO:0030020	Extracellular matrix structural constituent conferring tensile strength	–	0.000134592	0.000487548	Transitional
GO:0046872	Metal ion binding	0.001271416	–	0.001801895	Transitional
Cellular Component
GO:0005654	Nucleoplasm	8.01633E-10	8.15503E-10	0.002022821	Common Enrichment
GO:0005634	Nucleus	7.03725E-10	1.98908E-09	5.51924E-09	Common Enrichment
GO:0045178	Basal part of cell	–	0.000717997	0.000607947	Transitional
GO:0071944	Cell periphery	–	0.000126015	7.75437E-05	Transitional
GO:0005592	Collagen type XI trimer	0.002324111	–	0.00088074	Transitional
GO:0005730	Nucleolus	1.78313E-07	0.002198699	–	Unique in right lesions

Abbreviations: GO, Gene Ontology; LLL, left lower lobe; RML, right middle lobe; RLL, right lower lobe.

Figure 2 Transcriptome-assisted origin assessment of multiple ACC lesions. (A) The Venn diagram visualized the number of differential gene expression in the three tumors. (B) Heatmap of differential gene expression correlation matrices. (C) Hierarchical clustering and principal component analysis of gene expression profile. (D) KEGG signaling pathway analysis of DEGs in three tumors. Cells in green indicate the signaling pathways are significantly enriched, while cells in red mean the pathways are not activated.

Abbreviations: LLL, left lower lobe; RML, right middle lobe; RLL, right lower lobe; KEGG, Kyoto Encyclopedia of Genes and Genomes.