Universität zu Köln

Dietlein, Felix and Eschner, Wolfgang (2014). Inferring primary tumor sites from mutation spectra: a meta-analysis of histology-specific aberrations in cancer-derived cell lines. Hum. Mol. Genet., 23 (6). S. 1527 - 1538. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2083

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Abstract

Next-generation sequencing technologies have led to profound characterization of mutation spectra for several cancer types. Hence, we sought to systematically compare genomic aberrations between primary tumors and cancer lines. For this, we compiled publically available sequencing data of 1651 genes across 905 cell lines. We used them to characterize 23 distinct primary tumor sites by a novel approach that is based on Bayesian spam-filtering techniques. Thereby, we confirmed the strong overall similarity of alterations between patient samples and cell culture. However, we also identified several suspicious mutations, which had not been associated with their cancer types before. Based on these characterizations, we developed the inferring cancer origins from mutation spectra (ICOMS) tool. On our cell line collection, the algorithm reached a prediction specificity rate of 79%, which strongly variegated between primary cancer sites. On an independent validation cohort of 431 primary tumor samples, we observed a similar accuracy of 71%. Additionally, we found that ICOMS could be employed to deduce further attributes from mutation spectra, including sub-histology and compound sensitivity. Thus, thorough classification of site-specific mutation spectra for cell lines maydecipher further genome-phenotype associations in cancer.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dietlein, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Eschner, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-443359
DOI:	10.1093/hmg/ddt539
Journal or Publication Title:	Hum. Mol. Genet.
Volume:	23
Number:	6
Page Range:	S. 1527 - 1538
Date:	2014
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2083
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACUTE MYELOID-LEUKEMIA; EML4-ALK FUSION GENE; KRAS MUTATIONS; LUNG-CANCER; MOLECULAR CHARACTERIZATION; THYROTROPIN RECEPTOR; ACTIVATING MUTATIONS; PANCREATIC-CANCER; SOMATIC MUTATIONS; PTEN MUTATIONS Multiple languages Biochemistry & Molecular Biology; Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44335