Testing tumors from different anatomic sites for clonal relatedness using somatic mutation data Journal Article


Authors: Ostrovnaya, I.; Mauguen, A.; Seshan, V. E.; Begg, C. B.
Article Title: Testing tumors from different anatomic sites for clonal relatedness using somatic mutation data
Abstract: A common task for the cancer pathologist is to determine, in a patient suffering from cancer, whether a new tumor in a distinct anatomic site from the primary is an independent occurrence of cancer or a metastasis. As mutational profiling of tumors becomes more widespread in routine clinical practice, this diagnostic task can be greatly enhanced by comparing mutational profiles of the tumors to determine if they are sufficiently similar to conclude that the tumors are clonally related, that is, one is a metastasis of the other. We present here a likelihood ratio test for clonal relatedness in this setting and provide evidence of its validity. The test is unusual in that there are two possible alternative hypotheses, representing the two anatomic sites from which the single clonal cell could have initially emerged. Although evidence for clonal relatedness is largely provided by the presence of exact mutational matches in the two tumors, we show that it is possible to observe data where the test is statistically significant even when no matches are observed. This can occur when the mutational profile of one of the tumors is closely aligned with the anatomic site of the other tumor, suggesting indirectly that the tumor originated in that other site. We exhibit examples of this phenomenon and recommend a strategy for interpreting the results of these tests in practice. © 2020 The International Biometric Society
Keywords: mutation; metastasis; anatomy; diagnostic test; tumor; cell; clonality; testing method; cancer; genomic profiling; double primary
Journal Title: Biometrics
Volume: 77
Issue: 1
ISSN: 0006-341X
Publisher: Wiley Blackwell  
Date Published: 2021-03-01
Start Page: 283
End Page: 292
Language: English
DOI: 10.1111/biom.13256
PUBMED: 32135575
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 April 2021 -- Source: Scopus
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MSK Authors
  1. Venkatraman Ennapadam Seshan
    336 Seshan
  2. Colin B Begg
    280 Begg
  3. Audrey   Mauguen
    67 Mauguen