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Recurrent chromosomal copy number alterations in sporadic chordomas.

Le LP, Nielsen GP, Rosenberg AE, Thomas D, Batten JM, Deshpande V, Schwab J, Duan Z, Xavier RJ, Hornicek FJ, Iafrate AJ - PLoS ONE (2011)

Bottom Line: One copy loss of the 10q23.31 region which encodes PTEN was found in 16/20 (80%) cases.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. lple@partners.org

ABSTRACT
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.

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Heat map of array CGH results.Copy number gains (red) and losses (green) are displayed for each                            individual chordoma case (rows) with chromosomes organized in columns                            (separated by white vertical lines) and indicated by labels at the                            bottom. Note that cases CH34 and CH37 are recurrent tumors from the same                            patient.
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pone-0018846-g001: Heat map of array CGH results.Copy number gains (red) and losses (green) are displayed for each individual chordoma case (rows) with chromosomes organized in columns (separated by white vertical lines) and indicated by labels at the bottom. Note that cases CH34 and CH37 are recurrent tumors from the same patient.

Mentions: Comparative genomic hybridization using the Agilent 244K genome-wide oligonucleotide array showed predominantly copy number losses involving an average of 26.5±10.0% of the genome per case (16.5% to 56.6% range, excluding the Y chromosome, Figures 1 and 2). Copy number gains affected on average 7.1±7.2% of the genome per case (<0.1% to 27.1% range, excluding the Y chromosome), which is significantly less than involvement by copy number losses (P<0.01, Figures 1 and 2). Frequent whole chromosome changes included losses of chromosomes 3 (75%), 4 (40%), 9 (45%), 10 (75%), 13 (55%), 14 (55%), and 18 (40%). The most common chromosome gain involved chromosome 7 which was found in a total of 5 cases (25%).


Recurrent chromosomal copy number alterations in sporadic chordomas.

Le LP, Nielsen GP, Rosenberg AE, Thomas D, Batten JM, Deshpande V, Schwab J, Duan Z, Xavier RJ, Hornicek FJ, Iafrate AJ - PLoS ONE (2011)

Heat map of array CGH results.Copy number gains (red) and losses (green) are displayed for each                            individual chordoma case (rows) with chromosomes organized in columns                            (separated by white vertical lines) and indicated by labels at the                            bottom. Note that cases CH34 and CH37 are recurrent tumors from the same                            patient.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3094331&req=5

pone-0018846-g001: Heat map of array CGH results.Copy number gains (red) and losses (green) are displayed for each individual chordoma case (rows) with chromosomes organized in columns (separated by white vertical lines) and indicated by labels at the bottom. Note that cases CH34 and CH37 are recurrent tumors from the same patient.
Mentions: Comparative genomic hybridization using the Agilent 244K genome-wide oligonucleotide array showed predominantly copy number losses involving an average of 26.5±10.0% of the genome per case (16.5% to 56.6% range, excluding the Y chromosome, Figures 1 and 2). Copy number gains affected on average 7.1±7.2% of the genome per case (<0.1% to 27.1% range, excluding the Y chromosome), which is significantly less than involvement by copy number losses (P<0.01, Figures 1 and 2). Frequent whole chromosome changes included losses of chromosomes 3 (75%), 4 (40%), 9 (45%), 10 (75%), 13 (55%), 14 (55%), and 18 (40%). The most common chromosome gain involved chromosome 7 which was found in a total of 5 cases (25%).

Bottom Line: One copy loss of the 10q23.31 region which encodes PTEN was found in 16/20 (80%) cases.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. lple@partners.org

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus