Statistical Evaluation of Evidence for Clonal Allelic Alterations in array-CGH Experiments
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Abstract:
In recent years numerous investigators have conducted genetic studies of pairs of tumor specimens from the same patient to determine whether the tumors share a clonal origin. These studies have the potential to be of considerable clinical significance, especially in clinical settings where the distinction of a new primary cancer and metastatic spread of a previous cancer would lead to radically different indications for treatment. Studies of clonality have typically involved comparison of the patterns of somatic mutations in the tumors at candidate genetic loci to see if the patterns are sufficiently similar to indicate a clonal origin. More recently, some investigators have explored the use of array CGH for this purpose. Standard clustering approaches have been used to analyze the data, but these existing statistical methods are not suited to this problem due to the paired nature of the data, and the fact that there exists no “gold standard” diagnosis to provide a definitive determination of which pairs are clonal and which pairs are of independent origin. In this article we propose a new statistical method that focuses on the individual allelic gains or losses that have been identified in both tumors, and a statistical test is developed that assesses the degree of matching of the locations of the markers that indicate the endpoints of the allelic change. The validity and statistical power of the test is evaluated, and it is shown to be a promising approach for establishing clonality in tumor samples.
Subject Area:
Genetics, Microarrays
Suggested Citation:
Colin B. Begg, Kevin Eng, Adam Olshen, and E S. Venkatraman, "Statistical Evaluation of Evidence for Clonal Allelic Alterations in array-CGH Experiments" (March 2007). Memorial Sloan-Kettering Cancer Center Department of Epidemiology and Biostatistics Working Paper Series. Working Paper 13.
http://www.bepress.com/mskccbiostat/paper13