Here, we report the application of a long-read sequencer, PromethION, for analyzing human cancer genomes. We first conducted whole-genome sequencing on lung cancer cell lines. We found that it is possible to genotype known cancerous mutations, such as point mutations. We also found that long-read sequencing is particularly useful for precisely identifying and characterizing structural aberrations, such as large deletions, gene fusions, and other chromosomal rearrangements. In addition, we identified several medium-sized structural aberrations consisting of complex combinations of local duplications, inversions, and microdeletions. These complex mutations occurred even in key cancer-related genes, such as STK11, NF1, SMARCA4, and PTEN. The biological relevance of those mutations was further revealed by epigenome, transcriptome, and protein analyses of the affected signaling pathways. Such structural aberrations were also found in clinical lung adenocarcinoma specimens. Those structural aberrations were unlikely to be reliably detected by conventional short-read sequencing. Therefore, long-read sequencing may contribute to understanding the molecular etiology of patients for whom causative cancerous mutations remain unknown and therapeutic strategies are elusive.

Reference: Long-read sequencing for non-small-cell lung cancer genomes

Accession:JGAS00000000065 (JGAD00000000252 / JGAD00000000253)* Controlled Access.

	Tumor			Normal
sampleID	Yields(Gb)	Number of reads	Coverage(x)	Yields(Gb)	Number of reads	Coverage(x)	Number of SVs	Processed data
S1	99	14881240	33	57	11709609	19	7	S1_SV_gene_candidates.bedpe
S2	94	25379061	31	41	7016159	14	120	S2_SV_gene_candidates.bedpe
S3	77	15952312	25	48	12971173	15	41	S3_SV_gene_candidates.bedpe
S5	82	21640571	27	35	6503970	11	11	S5_SV_gene_candidates.bedpe
S6	76	11336329	25	48	7531078	16	72	S6_SV_gene_candidates.bedpe
S7	85	13880384	28	46	7555316	15	91	S7_SV_gene_candidates.bedpe
S8	100	18661003	33	54	8351411	18	67	S8_SV_gene_candidates.bedpe
S9	96	13179209	32	34	4483001	11	48	S9_SV_gene_candidates.bedpe
S10	85	12424087	28	42	7029224	14	64	S10_SV_gene_candidates.bedpe
S11	69	21140772	22	59	7832201	19	42	S11_SV_gene_candidates.bedpe
S12	73	15634853	24	84	12908975	27	2	S12_SV_gene_candidates.bedpe
S13	104	30719862	34	38	5506152	12	31	S13_SV_gene_candidates.bedpe
S14	74	14328017	24	56	6464828	18	53	S14_SV_gene_candidates.bedpe
S15	75	12278084	24	55	9585959	18	7	S15_SV_gene_candidates.bedpe
S16	74	20118226	24	55	7924757	18	103	S16_SV_gene_candidates.bedpe
S17	52	7086616	17	59	6766386	20	3	S17_SV_gene_candidates.bedpe
S18	62	7091142	20	44	5335320	15	14	S18_SV_gene_candidates.bedpe
S19	60	6352847	20	37	5025576	12	10	S19_SV_gene_candidates.bedpe
S20	58	5836744	19	47	5620346	15	87	S20_SV_gene_candidates.bedpe
S21	63	8985953	21	57	6166961	19	19	S21_SV_gene_candidates.bedpe

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RERF-LC-KJ: STK11

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RERF-LC-KJ: NF1

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PC-14: SMARCA4

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PC-14: PTEN

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