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September 2015 Using somatic mutation data to test tumors for clonal relatedness
Irina Ostrovnaya, Venkatraman E. Seshan, Colin B. Begg
Ann. Appl. Stat. 9(3): 1533-1548 (September 2015). DOI: 10.1214/15-AOAS836


A major challenge for cancer pathologists is to determine whether a new tumor in a patient with cancer is a metastasis or an independent occurrence of the disease. In recent years numerous studies have evaluated pairs of tumor specimens to examine the similarity of the somatic characteristics of the tumors and to test for clonal relatedness. As the landscape of mutation testing has evolved, a number of statistical methods for determining clonality have developed, notably for comparing losses of heterozygosity at candidate markers, and for comparing copy number profiles. Increasingly tumors are being evaluated for point mutations in panels of candidate genes using gene sequencing technologies. Comparison of the mutational profiles of pairs of tumors presents unusual methodological challenges: mutations at some loci are much more common than others; knowledge of the marginal mutation probabilities is scanty for most loci at which mutations might occur; the sample space of potential mutational profiles is vast. We examine this problem and propose a test for clonal relatedness of a pair of tumors from a single patient. Using simulations, its properties are shown to be promising. The method is illustrated using several examples from the literature.


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Irina Ostrovnaya. Venkatraman E. Seshan. Colin B. Begg. "Using somatic mutation data to test tumors for clonal relatedness." Ann. Appl. Stat. 9 (3) 1533 - 1548, September 2015.


Received: 1 March 2014; Revised: 1 May 2015; Published: September 2015
First available in Project Euclid: 2 November 2015

zbMATH: 06525997
MathSciNet: MR3418734
Digital Object Identifier: 10.1214/15-AOAS836

Rights: Copyright © 2015 Institute of Mathematical Statistics


Vol.9 • No. 3 • September 2015
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