Universität zu Köln

Kaya, Neslihan A., Chen, Jianbin, Lai, Hannah, Yang, Hechuan, Ma, Liang, Liu, Xiaodong ORCID: 0000-0001-5372-9709, Alvarez, Jacob Santiago, Liu, Jin ORCID: 0000-0002-5707-2078, Hillmer, Axel M., Tai, David, Sheng, Joe Yeong Poh, Hu, Zheng, Chan, Yun Shen, Chow, Pierce K. H., Mu, Yuguang, Wuestefeld, Torsten and Zhai, Weiwei (2022). Genome instability is associated with ethnic differences between Asians and Europeans in hepatocellular carcinoma. Theranostics, 12 (10). S. 4703 - 4718. LAKE HAVEN: IVYSPRING INT PUBL. ISSN 1838-7640

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Abstract

Y Hepatocellular carcinoma (HCC) is one of the deadliest cancer types with diverse etiological factors across the world. Although large scale genomic studies have been conducted in different countries, integrative analysis of HCC genomes and ethnic comparison across cohorts are lacking. Methods: We first integrated genomes of 1,349 HCC patients from five large cohorts across the world and applied multiple statistical methods in identifying driver genes. Subsequently, we systematically compared HCC genomes and transcriptomes between Asians and Europeans using the TCGA cohort. Results: We identified 29 novel candidate driver genes, many of which are infrequent tumor suppressors driving late-stage tumor progression. When we systematically compared ethnic differences in the genomic landscape between Asian and European HCCs using the TCGA cohort (n = 348), we found little differences in driver frequencies. Through multi-modal integrative analysis, we found higher genomic instability in Asians together with a collection of molecular events ranging from tumor mutation burden (TMB), copy number alterations as well as transcriptomic subtypes segregating distinctively between two ethnic backgrounds. Strikingly, we identified an Asian specific transcriptomic subtype with multiple ethnically enriched genomic alterations, in particular chromosome 16 deletion, leading to a clinically aggressive RNA subgroup unique to Asians. Integrating multi-modal information, we found that surviv al models predict patient prognosis much better in Asians than in Europeans, demonstrating a higher potential for precision medicine applications in Asia. Conclusion: For the first time, we have uncovered an unprecedented amount of genomic differences segregating distinctively across ethnicities in HCC and highlighted the importance of differential disease biology and management in HCC across ethnic backgrounds.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kaya, Neslihan A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chen, Jianbin UNSPECIFIED UNSPECIFIED UNSPECIFIED Lai, Hannah UNSPECIFIED UNSPECIFIED UNSPECIFIED Yang, Hechuan UNSPECIFIED UNSPECIFIED UNSPECIFIED Ma, Liang UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Xiaodong UNSPECIFIED orcid.org/0000-0001-5372-9709 UNSPECIFIED Alvarez, Jacob Santiago UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Jin UNSPECIFIED orcid.org/0000-0002-5707-2078 UNSPECIFIED Hillmer, Axel M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tai, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Sheng, Joe Yeong Poh UNSPECIFIED UNSPECIFIED UNSPECIFIED Hu, Zheng UNSPECIFIED UNSPECIFIED UNSPECIFIED Chan, Yun Shen UNSPECIFIED UNSPECIFIED UNSPECIFIED Chow, Pierce K. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mu, Yuguang UNSPECIFIED UNSPECIFIED UNSPECIFIED Wuestefeld, Torsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhai, Weiwei UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-693772
DOI:	10.7150/thno.71676
Journal or Publication Title:	Theranostics
Volume:	12
Number:	10
Page Range:	S. 4703 - 4718
Date:	2022
Publisher:	IVYSPRING INT PUBL
Place of Publication:	LAKE HAVEN
ISSN:	1838-7640
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COPY-NUMBER; INTRATUMOR HETEROGENEITY; MOLECULAR CLASSIFICATION; MUTATIONAL SIGNATURES; INTEGRATED ANALYSIS; GENETIC ANCESTRY; CANCER; PREDICTION; LANDSCAPE; DIVERSITY Multiple languages Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69377