  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.
