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Testing Whether Tumors from The Same Patient Are Related

Objective

The goal of this on-going project is to develop statistical techniques for clonality assessment, used to distinguish independent second primary cancers from metastases on the basis of the somatic molecular profiles of the tumors.
 

Project Members

Colin Begg
Audrey Mauguen
Irina Ostrovnaya
Venkat Seshan

 

Description

Patients with cancer frequently develop new tumors that may be metastases or independent occurrences of cancer. Determining whether the new tumor is a new cancer or a metastasis can have important clinical implications. We have been developing statistical techniques that interpret information from genetic tests to determine which clinical diagnosis is correct.

 

Software

The methods are implemented in the R/Bioconductor package Clonality
 

Publications

Statistical Methods

Mauguen A, Seshan VE, Ostrovnaya I, Begg CB. Estimating the probability of clonal relatedness of pairs of tumors in cancer patients. Biometrics. 2018 Mar;74(1):321-330. doi: 10.1111/biom.12710. Epub 2017 May 8. PMID: 28482133

Ostrovnaya I, Seshan VE, Begg CB. Using somatic mutation data to test tumors for clonal relatedness. Ann Appl Stat. 2015 Sep;9(3):1533-1548. Epub 2015 Nov 2.PMID:26594266

Ostrovnaya I. Testing clonality of three and more tumors using their loss of heterozygosity profiles. Stat Appl Genet Mol Biol. 2012 Jul 13;11(4). pii: /j/sagmb.2012.11.issue-4/1544-6115.1757/1544-6115.1757.xml. doi: 10.1515/1544-6115.1757. Review. PMID: 22850066

Ostrovnaya I, Seshan VE, Olshen AB, Begg CB. Clonality: an R package for testing clonal relatedness of two tumors from the same patient based on their genomic profiles. Bioinformatics. 2011 Jun 15;27(12):1698-9. doi: 10.1093/bioinformatics/btr267. Epub 2011 May 5. PMID:21546399

Ostrovnaya I, Olshen AB, Seshan VE, Orlow I, Albertson DG, Begg CB. A metastasis or a second independent cancer? Evaluating the clonal origin of tumors using array copy number data. Stat Med. 2010 Jul 10;29(15):1608-21. doi: 10.1002/sim.3866. PMID:20205270

Ostrovnaya I, Begg CB. Testing clonal relatedness of tumors using array comparative genomic hybridization: a statistical challenge. Clin Cancer Res. 2010 Mar 1;16(5):1358-67. doi: 10.1158/1078-0432.CCR-09-2398. Epub 2010 Feb 23. PMID:20179213

Ostrovnaya I, Seshan VE, Begg CB. Comparison of properties of tests for assessing tumor clonality. Biometrics. 2008 Dec;64(4):1018-22. doi: 10.1111/j.1541-0420.2008.00988.x. Epub 2008 Feb 11. PMID:18266893

Begg CB, Eng KH, Hummer AJ. Statistical tests for clonality. Biometrics. 2007 Jun;63(2):522-30. PMID:17688504

 

Applications

Begg CB, Ostrovnaya I, Geyer FC, Papanastasiou AD, Ng CKY, Sakr RA, Bernstein JL, Burke KA, King TA, Piscuoglio S, Mauguen A, Orlow I, Weigelt B, Seshan VE, Morrow M, Reis-Filho JS. Contralateral breast cancers: Independent cancers or metastases? Int J Cancer. 2018 Jan 15;142(2):347-356. doi: 10.1002/ijc.31051. Epub 2017 Sep 28. PMID: 28921573

Begg CB, Ostrovnaya I, Carniello JV, Sakr RA, Giri D, Towers R, Schizas M, De Brot M, Andrade VP, Mauguen A, Seshan VE, King TA. Clonal relationships between lobular carcinoma in situ and other breast malignancies. Breast Cancer Res. 2016 Jun 23;18(1):66. doi: 10.1186/s13058-016-0727-z. PMID:27334989

Andrade VP, Ostrovnaya I, Seshan VE, Morrogh M, Giri D, Olvera N, De Brot M, Morrow M, Begg CB, King TA. Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions. Breast Cancer Res. 2012 Jul 9;14(4):R103. doi: 10.1186/bcr3222. PMID:22776144

Girard N, Ostrovnaya I, Lau C, Park B, Ladanyi M, Finley D, Deshpande C, Rusch V, Orlow I, Travis WD, Pao W, Begg CB. Genomic and mutational profiling to assess clonal relationships between multiple non-small cell lung cancers. Clin Cancer Res. 2009 Aug 15;15(16):5184-90. doi: 10.1158/1078-0432.CCR-09-0594. Epub 2009 Aug 11. PMID:19671847

Orlow I, Tommasi DV, Bloom B, Ostrovnaya I, Cotignola J, Mujumdar U, Busam KJ, Jungbluth AA, Scolyer RA, Thompson JF, Armstrong BK, Berwick M, Thomas NE, Begg CB. Evaluation of the clonal origin of multiple primary melanomas using molecular profiling. J Invest Dermatol. 2009 Aug;129(8):1972-82. doi: 10.1038/jid.2009.4. Epub 2009 Mar 12. PMID:1928284