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A major challenge for cancer pathologists is to determine whether a new tumorin a patient with cancer is a metastasis or an independent occurrence of thedisease. In recent years numerous studies have evaluated pairs of tumorspecimens to examine the similarity of the somatic characteristics of thetumors and to test for clonal relatedness. As the landscape of mutation testinghas evolved, a number of statistical methods for determining clonality havedeveloped, notably for comparing losses of heterozygosity at candidate markers,and for comparing copy number profiles. Increasingly tumors are being evaluatedfor point mutations in panels of candidate genes using gene sequencingtechnologies. Comparison of the mutational profiles of pairs of tumors presentsunusual methodological challenges: mutations at some loci are much more commonthan others; knowledge of the marginal mutation probabilities is scanty formost loci at which mutations might occur; the sample space of potentialmutational profiles is vast. We examine this problem and propose a test forclonal relatedness of a pair of tumors from a single patient. Usingsimulations, its properties are shown to be promising. The method isillustrated using several examples from the literature.

Using somatic mutation data to test tumors for clonal relatedness