Clonality analysis of pulmonary tumors by genome-wide copy number profiling.
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 as...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0223827 |
| _version_ | 1819123679216271360 |
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| author | Julien P L Vincenten Hendrik F van Essen Birgit I Lissenberg-Witte Nicole W J Bulkmans Oscar Krijgsman Daoud Sie Paul P Eijk Egbert F Smit Bauke Ylstra Erik Thunnissen |
| author_facet | Julien P L Vincenten Hendrik F van Essen Birgit I Lissenberg-Witte Nicole W J Bulkmans Oscar Krijgsman Daoud Sie Paul P Eijk Egbert F Smit Bauke Ylstra Erik Thunnissen |
| author_sort | Julien P L Vincenten |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T07:12:11Z |
| format | Article |
| id | doaj.art-c088b4a2cc0b46bfa3d0b227870d4855 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T07:12:11Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-c088b4a2cc0b46bfa3d0b227870d48552022-12-21T18:34:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-011410e022382710.1371/journal.pone.0223827Clonality analysis of pulmonary tumors by genome-wide copy number profiling.Julien P L VincentenHendrik F van EssenBirgit I Lissenberg-WitteNicole W J BulkmansOscar KrijgsmanDaoud SiePaul P EijkEgbert F SmitBauke YlstraErik ThunnissenMultiple 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.https://doi.org/10.1371/journal.pone.0223827 |
| spellingShingle | Julien P L Vincenten Hendrik F van Essen Birgit I Lissenberg-Witte Nicole W J Bulkmans Oscar Krijgsman Daoud Sie Paul P Eijk Egbert F Smit Bauke Ylstra Erik Thunnissen Clonality analysis of pulmonary tumors by genome-wide copy number profiling. PLoS ONE |
| title | Clonality analysis of pulmonary tumors by genome-wide copy number profiling. |
| title_full | Clonality analysis of pulmonary tumors by genome-wide copy number profiling. |
| title_fullStr | Clonality analysis of pulmonary tumors by genome-wide copy number profiling. |
| title_full_unstemmed | Clonality analysis of pulmonary tumors by genome-wide copy number profiling. |
| title_short | Clonality analysis of pulmonary tumors by genome-wide copy number profiling. |
| title_sort | clonality analysis of pulmonary tumors by genome wide copy number profiling |
| url | https://doi.org/10.1371/journal.pone.0223827 |
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