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Genomic profiling of advanced-stage oral cancers reveals chromosome 11q alterations as markers of poor clinical outcome.

Ambatipudi S, Gerstung M, Gowda R, Pai P, Borges AM, Schäffer AA, Beerenwinkel N, Mahimkar MB - PLoS ONE (2011)

Bottom Line: Copy-number changes were observed on chromosomal arms with most frequent gains on 3q (60%), 5p (50%), 7p (50%), 8q (73%), 11q13 (47%), 14q11.2 (47%), and 19p13.3 (58%) and losses on 3p14.2 (55%) and 8p (83%).Univariate statistical analysis with correction for multiple testing revealed chromosomal gain of region 11q22.1-q22.2 and losses of 17p13.3 and 11q23-q25 to be associated with loco-regional recurrence (P = 0.004, P = 0.003, and P = 0.0003) and shorter survival (P = 0.009, P = 0.003, and P 0.0001) respectively.The gain of 11q22 and loss of 11q23-q25 were validated by interphase fluorescent in situ hybridization (I-FISH).

View Article: PubMed Central - PubMed

Affiliation: Tata Memorial Centre, Advanced Centre for Treatment, Research and Education in Cancer, Cancer Research Institute, Navi Mumbai, India.

ABSTRACT
Identifying oral cancer lesions associated with high risk of relapse and predicting clinical outcome remain challenging questions in clinical practice. Genomic alterations may add prognostic information and indicate biological aggressiveness thereby emphasizing the need for genome-wide profiling of oral cancers. High-resolution array comparative genomic hybridization was performed to delineate the genomic alterations in clinically annotated primary gingivo-buccal complex and tongue cancers (n = 60). The specific genomic alterations so identified were evaluated for their potential clinical relevance. Copy-number changes were observed on chromosomal arms with most frequent gains on 3q (60%), 5p (50%), 7p (50%), 8q (73%), 11q13 (47%), 14q11.2 (47%), and 19p13.3 (58%) and losses on 3p14.2 (55%) and 8p (83%). Univariate statistical analysis with correction for multiple testing revealed chromosomal gain of region 11q22.1-q22.2 and losses of 17p13.3 and 11q23-q25 to be associated with loco-regional recurrence (P = 0.004, P = 0.003, and P = 0.0003) and shorter survival (P = 0.009, P = 0.003, and P 0.0001) respectively. The gain of 11q22 and loss of 11q23-q25 were validated by interphase fluorescent in situ hybridization (I-FISH). This study identifies a tractable number of genomic alterations with few underlying genes that may potentially be utilized as biological markers for prognosis and treatment decisions in oral cancers.

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Radial heatmap of recurring copy-number alterations (CNAs) in OSCC.Shown in the inner heatmap are copy number gains/amplifications (blue) and losses/deletions (red), where tumors are stacked radially. Significantly recurring alterations (RAE q-value <0.1) are displayed between the outermost chromosome ideograms and the inner heat map (red: losses, blue: gains). Open circles denote known copy-number variants (CNVs) that span more than 50% with recurring CNAs. Chromosome numbers are shown in bold at periphery of chromosome ideograms with genomic coordinates in megabases.
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pone-0017250-g001: Radial heatmap of recurring copy-number alterations (CNAs) in OSCC.Shown in the inner heatmap are copy number gains/amplifications (blue) and losses/deletions (red), where tumors are stacked radially. Significantly recurring alterations (RAE q-value <0.1) are displayed between the outermost chromosome ideograms and the inner heat map (red: losses, blue: gains). Open circles denote known copy-number variants (CNVs) that span more than 50% with recurring CNAs. Chromosome numbers are shown in bold at periphery of chromosome ideograms with genomic coordinates in megabases.

Mentions: RAE analysis was performed to identify recurring disease-associated chromosomal aberrations and segregate them from neutral ones. At a false discovery rate of q = 0.1, a total of 93 distinct CNAs were found by the RAE algorithm (Figure 1; Figure S2), seven of which in the centromeric regions; for 13 CNAs an additional localized peak region was detected (Table S2). Non-centromeric chromosomal aberrations occurring in more than 20% of the cases are presented in Tables 2 and 3. A large fraction of samples show gross whole chromosome-level alterations (Figure 1). Overall, the number of chromosomal losses (n = 61, including 7 centromeric) was higher than the number of gains (n = 32), but the difference was smaller for high-frequency CNAs (n = 35 versus n = 30). The detailed list of “candidate genes” for all the regions found altered is presented in Table S2.


Genomic profiling of advanced-stage oral cancers reveals chromosome 11q alterations as markers of poor clinical outcome.

Ambatipudi S, Gerstung M, Gowda R, Pai P, Borges AM, Schäffer AA, Beerenwinkel N, Mahimkar MB - PLoS ONE (2011)

Radial heatmap of recurring copy-number alterations (CNAs) in OSCC.Shown in the inner heatmap are copy number gains/amplifications (blue) and losses/deletions (red), where tumors are stacked radially. Significantly recurring alterations (RAE q-value <0.1) are displayed between the outermost chromosome ideograms and the inner heat map (red: losses, blue: gains). Open circles denote known copy-number variants (CNVs) that span more than 50% with recurring CNAs. Chromosome numbers are shown in bold at periphery of chromosome ideograms with genomic coordinates in megabases.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046132&req=5

pone-0017250-g001: Radial heatmap of recurring copy-number alterations (CNAs) in OSCC.Shown in the inner heatmap are copy number gains/amplifications (blue) and losses/deletions (red), where tumors are stacked radially. Significantly recurring alterations (RAE q-value <0.1) are displayed between the outermost chromosome ideograms and the inner heat map (red: losses, blue: gains). Open circles denote known copy-number variants (CNVs) that span more than 50% with recurring CNAs. Chromosome numbers are shown in bold at periphery of chromosome ideograms with genomic coordinates in megabases.
Mentions: RAE analysis was performed to identify recurring disease-associated chromosomal aberrations and segregate them from neutral ones. At a false discovery rate of q = 0.1, a total of 93 distinct CNAs were found by the RAE algorithm (Figure 1; Figure S2), seven of which in the centromeric regions; for 13 CNAs an additional localized peak region was detected (Table S2). Non-centromeric chromosomal aberrations occurring in more than 20% of the cases are presented in Tables 2 and 3. A large fraction of samples show gross whole chromosome-level alterations (Figure 1). Overall, the number of chromosomal losses (n = 61, including 7 centromeric) was higher than the number of gains (n = 32), but the difference was smaller for high-frequency CNAs (n = 35 versus n = 30). The detailed list of “candidate genes” for all the regions found altered is presented in Table S2.

Bottom Line: Copy-number changes were observed on chromosomal arms with most frequent gains on 3q (60%), 5p (50%), 7p (50%), 8q (73%), 11q13 (47%), 14q11.2 (47%), and 19p13.3 (58%) and losses on 3p14.2 (55%) and 8p (83%).Univariate statistical analysis with correction for multiple testing revealed chromosomal gain of region 11q22.1-q22.2 and losses of 17p13.3 and 11q23-q25 to be associated with loco-regional recurrence (P = 0.004, P = 0.003, and P = 0.0003) and shorter survival (P = 0.009, P = 0.003, and P 0.0001) respectively.The gain of 11q22 and loss of 11q23-q25 were validated by interphase fluorescent in situ hybridization (I-FISH).

View Article: PubMed Central - PubMed

Affiliation: Tata Memorial Centre, Advanced Centre for Treatment, Research and Education in Cancer, Cancer Research Institute, Navi Mumbai, India.

ABSTRACT
Identifying oral cancer lesions associated with high risk of relapse and predicting clinical outcome remain challenging questions in clinical practice. Genomic alterations may add prognostic information and indicate biological aggressiveness thereby emphasizing the need for genome-wide profiling of oral cancers. High-resolution array comparative genomic hybridization was performed to delineate the genomic alterations in clinically annotated primary gingivo-buccal complex and tongue cancers (n = 60). The specific genomic alterations so identified were evaluated for their potential clinical relevance. Copy-number changes were observed on chromosomal arms with most frequent gains on 3q (60%), 5p (50%), 7p (50%), 8q (73%), 11q13 (47%), 14q11.2 (47%), and 19p13.3 (58%) and losses on 3p14.2 (55%) and 8p (83%). Univariate statistical analysis with correction for multiple testing revealed chromosomal gain of region 11q22.1-q22.2 and losses of 17p13.3 and 11q23-q25 to be associated with loco-regional recurrence (P = 0.004, P = 0.003, and P = 0.0003) and shorter survival (P = 0.009, P = 0.003, and P 0.0001) respectively. The gain of 11q22 and loss of 11q23-q25 were validated by interphase fluorescent in situ hybridization (I-FISH). This study identifies a tractable number of genomic alterations with few underlying genes that may potentially be utilized as biological markers for prognosis and treatment decisions in oral cancers.

Show MeSH
Related in: MedlinePlus