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Clonality analysis of pulmonary tumors by genome-wide copy number profiling.
PLoS One. 2019; 14(10):e0223827.Plos

Abstract

Multiple tumors in patients are frequently diagnosed, either synchronous or metachronous. The distinction between a second primary and a metastasis is important for treatment. Chromosomal DNA copy number aberrations (CNA) patterns are highly unique to specific tumors. The aim of this study was to assess genome-wide CNA-patterns as method to identify clonally related tumors in a prospective cohort of patients with synchronous or metachronous tumors, with at least one intrapulmonary tumor. In total, 139 tumor pairs from 90 patients were examined: 35 synchronous and 104 metachronous pairs. Results of CNA were compared to histological type, clinicopathological methods (Martini-Melamed-classification (MM) and ACCP-2013-criteria), and, if available, EGFR- and KRAS-mutation analysis. CNA-results were clonal in 74 pairs (53%), non-clonal in 33 pairs (24%), and inconclusive in 32 pairs (23%). Histological similarity was found in 130 pairs (94%). Concordance between histology and conclusive CNA-results was 69% (74 of 107 pairs: 72 clonal and two non-clonal). In 31 of 103 pairs with similar histology, genetics revealed non-clonality. In two out of four pairs with non-matching histology, genetics revealed clonality. The subgroups of synchronous and metachronous pairs showed similar outcome for the comparison of histological versus CNA-results. MM-classification and ACCP-2013-criteria, applicable on 34 pairs, and CNA-results were concordant in 50% and 62% respectively. Concordance between mutation matching and conclusive CNA-results was 89% (8 of 9 pairs: six clonal and two non-clonal). Interestingly, in one patient both tumors had the same KRAS mutation, but the CNA result was non-clonal. In conclusion, although some concordance between histological comparison and CNA profiling is present, arguments exist to prefer extensive molecular testing to determine whether a second tumor is a metastasis or a second primary.

Authors+Show Affiliations

Amsterdam UMC, location VUmc, Department of Pulmonary Diseases, Amsterdam, The Netherlands. Albert Schweitzer Hospital, Department of Pulmonary Diseases, Dordrecht, The Netherlands.Amsterdam UMC, location VUmc, Tumor Genome Analysis Core, Cancer Center Amsterdam, The Netherlands.Amsterdam UMC, location VUmc, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands.Spaarne Gasthuis, Department of Pathology, Haarlem, The Netherlands.Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Molecular Oncology & Immunology, Amsterdam, The Netherlands.Amsterdam UMC, location VUmc, Tumor Genome Analysis Core, Cancer Center Amsterdam, The Netherlands.Amsterdam UMC, location VUmc, Tumor Genome Analysis Core, Cancer Center Amsterdam, The Netherlands.Amsterdam UMC, location VUmc, Department of Pulmonary Diseases, Amsterdam, The Netherlands. Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Thoracic Oncology, Amsterdam, The Netherlands.Amsterdam UMC, location VUmc, Tumor Genome Analysis Core, Cancer Center Amsterdam, The Netherlands.Amsterdam UMC, location VUmc, Department of Pathology, Amsterdam, The Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31618260

Citation

Vincenten, Julien P L., et al. "Clonality Analysis of Pulmonary Tumors By Genome-wide Copy Number Profiling." PloS One, vol. 14, no. 10, 2019, pp. e0223827.
Vincenten JPL, van Essen HF, Lissenberg-Witte BI, et al. Clonality analysis of pulmonary tumors by genome-wide copy number profiling. PLoS ONE. 2019;14(10):e0223827.
Vincenten, J. P. L., van Essen, H. F., Lissenberg-Witte, B. I., Bulkmans, N. W. J., Krijgsman, O., Sie, D., Eijk, P. P., Smit, E. F., Ylstra, B., & Thunnissen, E. (2019). Clonality analysis of pulmonary tumors by genome-wide copy number profiling. PloS One, 14(10), e0223827. https://doi.org/10.1371/journal.pone.0223827
Vincenten JPL, et al. Clonality Analysis of Pulmonary Tumors By Genome-wide Copy Number Profiling. PLoS ONE. 2019;14(10):e0223827. PubMed PMID: 31618260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clonality analysis of pulmonary tumors by genome-wide copy number profiling. AU - Vincenten,Julien P L, AU - van Essen,Hendrik F, AU - Lissenberg-Witte,Birgit I, AU - Bulkmans,Nicole W J, AU - Krijgsman,Oscar, AU - Sie,Daoud, AU - Eijk,Paul P, AU - Smit,Egbert F, AU - Ylstra,Bauke, AU - Thunnissen,Erik, Y1 - 2019/10/16/ PY - 2019/01/14/received PY - 2019/09/30/accepted PY - 2019/10/17/entrez PY - 2019/10/17/pubmed PY - 2020/3/17/medline SP - e0223827 EP - e0223827 JF - PloS one JO - PLoS ONE VL - 14 IS - 10 N2 - Multiple tumors in patients are frequently diagnosed, either synchronous or metachronous. The distinction between a second primary and a metastasis is important for treatment. Chromosomal DNA copy number aberrations (CNA) patterns are highly unique to specific tumors. The aim of this study was to assess genome-wide CNA-patterns as method to identify clonally related tumors in a prospective cohort of patients with synchronous or metachronous tumors, with at least one intrapulmonary tumor. In total, 139 tumor pairs from 90 patients were examined: 35 synchronous and 104 metachronous pairs. Results of CNA were compared to histological type, clinicopathological methods (Martini-Melamed-classification (MM) and ACCP-2013-criteria), and, if available, EGFR- and KRAS-mutation analysis. CNA-results were clonal in 74 pairs (53%), non-clonal in 33 pairs (24%), and inconclusive in 32 pairs (23%). Histological similarity was found in 130 pairs (94%). Concordance between histology and conclusive CNA-results was 69% (74 of 107 pairs: 72 clonal and two non-clonal). In 31 of 103 pairs with similar histology, genetics revealed non-clonality. In two out of four pairs with non-matching histology, genetics revealed clonality. The subgroups of synchronous and metachronous pairs showed similar outcome for the comparison of histological versus CNA-results. MM-classification and ACCP-2013-criteria, applicable on 34 pairs, and CNA-results were concordant in 50% and 62% respectively. Concordance between mutation matching and conclusive CNA-results was 89% (8 of 9 pairs: six clonal and two non-clonal). Interestingly, in one patient both tumors had the same KRAS mutation, but the CNA result was non-clonal. In conclusion, although some concordance between histological comparison and CNA profiling is present, arguments exist to prefer extensive molecular testing to determine whether a second tumor is a metastasis or a second primary. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/31618260/Clonality_analysis_of_pulmonary_tumors_by_genome-wide_copy_number_profiling L2 - http://dx.plos.org/10.1371/journal.pone.0223827 DB - PRIME DP - Unbound Medicine ER -