Recurrent chromosomal copy number alterations in sporadic chordomas.
The molecular events in chordoma pathogenesis have not been fully delineated, particularly with respect to copy number changes. Understanding copy number alterations in chordoma may reveal critical disease mechanisms that could be exploited for tumor classification and therapy. We report the copy nu...
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0018846&type=printable |
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| author | Long Phi Le G Petur Nielsen Andrew Eric Rosenberg Dafydd Thomas Julie M Batten Vikram Deshpande Joseph Schwab Zhenfeng Duan Ramnik J Xavier Francis J Hornicek A John Iafrate |
| author_facet | Long Phi Le G Petur Nielsen Andrew Eric Rosenberg Dafydd Thomas Julie M Batten Vikram Deshpande Joseph Schwab Zhenfeng Duan Ramnik J Xavier Francis J Hornicek A John Iafrate |
| author_sort | Long Phi Le |
| collection | DOAJ |
| description | The molecular events in chordoma pathogenesis have not been fully delineated, particularly with respect to copy number changes. Understanding copy number alterations in chordoma may reveal critical disease mechanisms that could be exploited for tumor classification and therapy. We report the copy number analysis of 21 sporadic chordomas using array comparative genomic hybridization (CGH). Recurrent copy changes were further evaluated with immunohistochemistry, methylation specific PCR, and quantitative real-time PCR. Similar to previous findings, large copy number losses, involving chromosomes 1p, 3, 4, 9, 10, 13, 14, and 18, were more common than copy number gains. Loss of CDKN2A with or without loss of CDKN2B on 9p21.3 was observed in 16/20 (80%) unique cases of which six (30%) showed homozygous deletions ranging from 76 kilobases to 4.7 megabases. One copy loss of the 10q23.31 region which encodes PTEN was found in 16/20 (80%) cases. Loss of CDKN2A and PTEN expression in the majority of cases was not attributed to promoter methylation. Our sporadic chordoma cases did not show hotspot point mutations in some common cancer gene targets. Moreover, most of these sporadic tumors are not associated with T (brachyury) duplication or amplification. Deficiency of CDKN2A and PTEN expression, although shared across many other different types of tumors, likely represents a key aspect of chordoma pathogenesis. Sporadic chordomas may rely on mechanisms other than copy number gain if they indeed exploit T/brachyury for proliferation. |
| format | Article |
| id | doaj-art-bec8012c458f46d88c33bf8f78abf689 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
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| spelling | doaj-art-bec8012c458f46d88c33bf8f78abf6892025-08-20T02:08:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0165e1884610.1371/journal.pone.0018846Recurrent chromosomal copy number alterations in sporadic chordomas.Long Phi LeG Petur NielsenAndrew Eric RosenbergDafydd ThomasJulie M BattenVikram DeshpandeJoseph SchwabZhenfeng DuanRamnik J XavierFrancis J HornicekA John IafrateThe molecular events in chordoma pathogenesis have not been fully delineated, particularly with respect to copy number changes. Understanding copy number alterations in chordoma may reveal critical disease mechanisms that could be exploited for tumor classification and therapy. We report the copy number analysis of 21 sporadic chordomas using array comparative genomic hybridization (CGH). Recurrent copy changes were further evaluated with immunohistochemistry, methylation specific PCR, and quantitative real-time PCR. Similar to previous findings, large copy number losses, involving chromosomes 1p, 3, 4, 9, 10, 13, 14, and 18, were more common than copy number gains. Loss of CDKN2A with or without loss of CDKN2B on 9p21.3 was observed in 16/20 (80%) unique cases of which six (30%) showed homozygous deletions ranging from 76 kilobases to 4.7 megabases. One copy loss of the 10q23.31 region which encodes PTEN was found in 16/20 (80%) cases. Loss of CDKN2A and PTEN expression in the majority of cases was not attributed to promoter methylation. Our sporadic chordoma cases did not show hotspot point mutations in some common cancer gene targets. Moreover, most of these sporadic tumors are not associated with T (brachyury) duplication or amplification. Deficiency of CDKN2A and PTEN expression, although shared across many other different types of tumors, likely represents a key aspect of chordoma pathogenesis. Sporadic chordomas may rely on mechanisms other than copy number gain if they indeed exploit T/brachyury for proliferation.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0018846&type=printable |
| spellingShingle | Long Phi Le G Petur Nielsen Andrew Eric Rosenberg Dafydd Thomas Julie M Batten Vikram Deshpande Joseph Schwab Zhenfeng Duan Ramnik J Xavier Francis J Hornicek A John Iafrate Recurrent chromosomal copy number alterations in sporadic chordomas. PLoS ONE |
| title | Recurrent chromosomal copy number alterations in sporadic chordomas. |
| title_full | Recurrent chromosomal copy number alterations in sporadic chordomas. |
| title_fullStr | Recurrent chromosomal copy number alterations in sporadic chordomas. |
| title_full_unstemmed | Recurrent chromosomal copy number alterations in sporadic chordomas. |
| title_short | Recurrent chromosomal copy number alterations in sporadic chordomas. |
| title_sort | recurrent chromosomal copy number alterations in sporadic chordomas |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0018846&type=printable |
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