Back to Journals » Advances in Genomics and Genetics » Volume 4

Whole exome sequencing for cancer – is there evidence of clinical utility?

Authors Malhotra A, Levine S, Allingham-Hawkins D

Received 27 March 2014

Accepted for publication 13 May 2014

Published 22 August 2014 Volume 2014:4 Pages 115—128


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Video abstract presented by Diane Allingham-Hawkins.

Views: 165

Alka Malhotra, Susan Levine, Diane Allingham-Hawkins

Genetic Test Evaluation Program, Winifred S Hayes, Inc., Lansdale, PA, USA

Background: In recent years, whole exome sequencing (WES), which allows detection of 85% of disease-causing variants, has been used to compare tumor and normal DNA to allow the identification of variants specific to the tumor. Genetic changes in cancer are increasingly used for diagnosis and may guide treatment decisions. In this paper, we explore whether there is evidence that WES improves outcomes for patients with cancer.
Methods: Published evidence was evaluated using a methodology that combines the analytical validity, clinical validity, clinical utility and ethical, legal, and social implications (ACCE) model for genetic test evaluations with internationally accepted health technology assessment methodology. Conclusions were based on peer-reviewed published studies of >10 patients, with ≥3 studies for a given phenotype.
Results: WES has been conducted most extensively (seven studies to date) in breast cancer patients, with fewer studies of other types of cancers (eg, leukemia, prostate cancer, and ovarian cancer). Studies evaluating somatic alterations showed high intratumor and intertumor heterogeneity. In addition, both novel and previously implicated variants were identified. However, only three studies with >10 individuals have shown potential for clinical utility of WES; whereby, variants identified through WES may determine response to drug treatment.
Conclusion: Despite evidence for clinical validity of WES in cancers, clinical utility is very limited and needs to be further evaluated in large clinical studies.

Keywords: next-generation sequencing, exons, evidence-based, ACCE model, health technology assessment

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]


Readers of this article also read:

Emerging and future therapies for hemophilia

Carr ME, Tortella BJ

Journal of Blood Medicine 2015, 6:245-255

Published Date: 3 September 2015

A new recombinant factor VIII: from genetics to clinical use

Santagostino E

Drug Design, Development and Therapy 2014, 8:2507-2515

Published Date: 12 December 2014

Green synthesis of water-soluble nontoxic polymeric nanocomposites containing silver nanoparticles

Prozorova GF, Pozdnyakov AS, Kuznetsova NP, Korzhova SA, Emel’yanov AI, Ermakova TG, Fadeeva TV, Sosedova LM

International Journal of Nanomedicine 2014, 9:1883-1889

Published Date: 16 April 2014

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone

Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W

International Journal of Nanomedicine 2012, 7:5719-5724

Published Date: 12 November 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010