Advertisement

Topics

Passenger mutations accurately classify human tumors.

08:00 EDT 15th April 2019 | BioPortfolio

Summary of "Passenger mutations accurately classify human tumors."

Determining the cancer type and molecular subtype has important clinical implications. The primary site is however unknown for some malignancies discovered in the metastatic stage. Moreover liquid biopsies may be used to screen for tumoral DNA, which upon detection needs to be assigned to a site-of-origin. Classifiers based on genomic features are a promising approach to prioritize the tumor anatomical site, type and subtype. We examined the predictive ability of causal (driver) somatic mutations in this task, comparing it against global patterns of non-selected (passenger) mutations, including features based on regional mutation density (RMD). In the task of distinguishing 18 cancer types, the driver mutations-mutated oncogenes or tumor suppressors, pathways and hotspots-classified 36% of the patients to the correct cancer type. In contrast, the features based on passenger mutations did so at 92% accuracy, with similar contribution from the RMD and the trinucleotide mutation spectra. The RMD and the spectra covered distinct sets of patients with predictions. In particular, introducing the RMD features into a combined classification model increased the fraction of diagnosed patients by 50 percentage points (at 20% FDR). Furthermore, RMD was able to discriminate molecular subtypes and/or anatomical site of six major cancers. The advantage of passenger mutations was upheld under high rates of false negative mutation calls and with exome sequencing, even though overall accuracy decreased. We suggest whole genome sequencing is valuable for classifying tumors because it captures global patterns emanating from mutational processes, which are informative of the underlying tumor biology.

Affiliation

Journal Details

This article was published in the following journal.

Name: PLoS computational biology
ISSN: 1553-7358
Pages: e1006953

Links

DeepDyve research library

PubMed Articles [16596 Associated PubMed Articles listed on BioPortfolio]

dbCPM: a manually curated database for exploring the cancer passenger mutations.

While recently emergent driver mutation data sets are available for developing computational methods to predict cancer mutation effects, benchmark sets focusing on passenger mutations are largely miss...

Heterogeneous mutational profile and prognosis conferred by TP53 mutations in Appendiceal mucinous neoplasms.

The 8th edition of American Joint Committee on Cancer (AJCC) advocates a three-tier grading system for appendiceal mucinous tumors. The mutational profile for each tumor grade and the impact of TP53 m...

Co-mutation and exclusion analysis in human tumors, a tool for cancer biology studies and for rational selection of multitargeted therapeutic approaches.

Malignant tumors originate from somatic mutations and other genomic and epigenomic alterations, which lead to loss of control of the cellular circuitry. These alterations present patterns of co-occurr...

Remodeling the cancer epigenome: mutations in the SWI/SNF complex offer new therapeutic opportunities.

Cancer genome sequencing studies have discovered mutations in members of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex in nearly 25% of human cancers. The SWI/SNF complex, ...

Landscape of germline and somatic mitochondrial DNA mutations in pediatric malignancies.

Little is known about the spectrum of mitochondrial DNA (mtDNA) mutations across pediatric malignancies. In this study, we analyzed matched tumor and normal whole genome sequencing data from 616 pedia...

Clinical Trials [7910 Associated Clinical Trials listed on BioPortfolio]

A Study of TAS-116 in Patients With Solid Tumors

A First-in-Human (FIH) study of TAS-116 in patients with advanced solid tumors was first initiated in Japan in April 2014 and has been ongoing since then. The study consists of a dose esca...

A Brief MI Intervention in the ED to Increase Child Passenger Restraint Use

This study involves an emergency department (ED)-based intervention utilizing Motivational Interviewing (MI) techniques and patient-centered (e.g., tailored) print materials to promote the...

Treatment With Dasatinib in Patients With Acral Lentiginous, Mucosal, or Chronic Sun-damaged Melanoma

The goal of this clinical research study is to compare how the drug Sprycel (dasatinib) can help to control the tumor in patients whose tumor has a gene abnormality known as a "CKIT mutati...

CB-839 HCl in Treating Patients With Specific Genetic Mutations and Metastatic or Unresectable Solid Tumors or Malignant Peripheral Nerve Sheath Tumors

This phase II trial studies how well glutaminase inhibitor CB-839 hydrochloride (CB-839 HCl) works in treating patients with specific genetic mutations and solid tumors or malignant periph...

Video-Based Social Learning or Didactics for Car Seat Education

This study compares a video-based social learning method to the traditional didactic method as a new way to teach caregivers about child passenger safety, including how to install a car se...

Medical and Biotech [MESH] Definitions

Transforming protein encoded by ras oncogenes. Point mutations in the cellular ras gene (c-ras) can also result in a mutant p21 protein that can transform mammalian cells. Oncogene protein p21(ras) has been directly implicated in human neoplasms, perhaps accounting for as much as 15-20% of all human tumors. This enzyme was formerly listed as EC 3.6.1.47.

A type of human papillomavirus especially associated with malignant tumors of the genital and RESPIRATORY MUCOSA.

Selective perceiving such that the individual protects himself from becoming aware of something unpleasant or threatening, e.g., obscene words are not heard correctly, or violent acts are not seen accurately.

Using MOLECULAR BIOLOGY techniques, such as DNA SEQUENCE ANALYSIS; PULSED-FIELD GEL ELECTROPHORESIS; and DNA FINGERPRINTING, to identify, classify, and compare organisms and their subtypes.

Mutations in genes which lead to cell or organism death when occurring in combination with mutations in one or more other genes.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Cancer Disease
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...


Searches Linking to this Article