Year: 2015
Type: article
Abstract: 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. In this article 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.
Source: The Annals of Applied Statistics
DOI: 10.1214/15-aoas836
Authors: Irina Ostrovnaya, Venkatraman E. Seshan, Colin B. Begg
Institution: Memorial Sloan Kettering Cancer Center
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2196993333