Testing clonality of three and more tumors using their loss of heterozygosity profiles

Ostrovnaya Irina
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Ostrovnaya Irina: Memorial Sloan-Kettering Cancer Center

Statistical Applications in Genetics and Molecular Biology, 2012, vol. 11, issue 4, 30

Abstract: Cancer patients often develop multiple malignancies that may be either metastatic spread of a previous cancer (clonal tumors) or new primary cancers (independent tumors). If diagnosis cannot be easily made on the basis of the pathology review, the patterns of somatic mutations in the tumors can be compared. Previously we have developed statistical methods for testing clonality of two tumors using their loss of heterozygosity (LOH) profiles at several candidate markers. These methods can be applied to all possible pairs of tumors when multiple tumors are analyzed, but this strategy can lead to inconsistent results and loss of statistical power. In this work we will extend clonality tests to three and more malignancies from the same patient. A non-parametric test can be performed using any possible subset of tumors, with the subsequent adjustment for multiple testing. A parametric likelihood model is developed for 3 or 4 tumors, and it can be used to estimate the phylogenetic tree of tumors. The proposed tests are more powerful than combination of all possible pairwise tests.

Keywords: clonality; LOH; metastasis; multiple tumors; concordant mutations test; likelihood ratio test (search for similar items in EconPapers)
Date: 2012
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DOI: 10.1515/1544-6115.1757

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