Cancer subtype identification using somatic mutation data.

British Journal of Cancer
Marieke Lydia KuijjerJohn Quackenbush

Abstract

With the onset of next-generation sequencing technologies, we have made great progress in identifying recurrent mutational drivers of cancer. As cancer tissues are now frequently screened for specific sets of mutations, a large amount of samples has become available for analysis. Classification of patients with similar mutation profiles may help identifying subgroups of patients who might benefit from specific types of treatment. However, classification based on somatic mutations is challenging due to the sparseness and heterogeneity of the data. Here we describe a new method to de-sparsify somatic mutation data using biological pathways. We applied this method to 23 cancer types from The Cancer Genome Atlas, including samples from 5805 primary tumours. We show that, for most cancer types, de-sparsified mutation data associate with phenotypic data. We identify poor prognostic subtypes in three cancer types, which are associated with mutations in signal transduction pathways for which targeted treatment options are available. We identify subtype-drug associations for 14 additional subtypes. Finally, we perform a pan-cancer subtyping analysis and identify nine pan-cancer subtypes, which associate with mutations in four overarchin...Continue Reading

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Citations

Apr 16, 2019·PLoS Computational Biology·Marina SalvadoresFran Supek
Jan 24, 2020·PLoS Biology·Charles BlattiSaurabh Sinha
Jan 24, 2020·International Journal of Cancer. Journal International Du Cancer·Tilmann BochtlerAlwin Krämer
Dec 14, 2019·Scientific Reports·Hamid TeimouriAnatoly B Kolomeisky
Nov 14, 2019·BMC Cancer·Manuela SalvucciJochen H M Prehn
Dec 17, 2020·Frontiers in Genetics·Narjes Rohani, Changiz Eslahchi
Mar 7, 2021·Biomolecules·Caterina MancarellaKatia Scotlandi
Jul 22, 2021·Bioinformatics·Cheng LiangJiawei Luo
Sep 9, 2021·Cancer Research·Camila M Lopes-RamosMarieke L Kuijjer
Sep 10, 2019·Journal of Biomedical Informatics·Olga LyudovykChunhua Weng

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Methods Mentioned

BETA
Protein Array
Exome Sequencing
PCA

Software Mentioned

Firehose
CGP
RTCGAToolbox
SAMBAR
R package RTCGA . RPPA
CMap
Connectivity Map ( CMap )
Pathway Commons

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