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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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Related in: MedlinePlus

Patient survival curves and FISH validation of 11q22.1-q22.2 gain.A) Kaplan-Meier survival estimates of patient groups with and without gain of chromosome 11q22.1–q22.2; survival in months (x-axis) is plotted against the fraction of samples alive (y-axis). Interphase FISH analysis detecting the chromosome 11 centromere (red) and the 11q22.1–q22.2 region (green), B) A case without 11q22.1-q22.2 gain and C) A case of 11q22.1–q22.2 gain are shown.
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pone-0017250-g004: Patient survival curves and FISH validation of 11q22.1-q22.2 gain.A) Kaplan-Meier survival estimates of patient groups with and without gain of chromosome 11q22.1–q22.2; survival in months (x-axis) is plotted against the fraction of samples alive (y-axis). Interphase FISH analysis detecting the chromosome 11 centromere (red) and the 11q22.1–q22.2 region (green), B) A case without 11q22.1-q22.2 gain and C) A case of 11q22.1–q22.2 gain are shown.

Mentions: Loss of 11q23–q25 (P = 0.0001) and gain of 11q22.1–q22.2 (P = 0.009) were found as the strongest predictors of poor clinical outcome in terms of recurrence and survival (Table 4). Kaplan-Meier survival curves for loss of distal 11q and gain of 11q22.1-q22.2 are shown in Figures 3A and 4A. The chromosomal interval 11q23–q25 was subdivided by RAE into four non-overlapping intervals. The p-values for the four association tests were almost identical, but the subdivision suggests that there were multiple pertinent genes on 11q23–q25, at least one gene per subinterval.


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)

Patient survival curves and FISH validation of 11q22.1-q22.2 gain.A) Kaplan-Meier survival estimates of patient groups with and without gain of chromosome 11q22.1–q22.2; survival in months (x-axis) is plotted against the fraction of samples alive (y-axis). Interphase FISH analysis detecting the chromosome 11 centromere (red) and the 11q22.1–q22.2 region (green), B) A case without 11q22.1-q22.2 gain and C) A case of 11q22.1–q22.2 gain are shown.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3046132&req=5

pone-0017250-g004: Patient survival curves and FISH validation of 11q22.1-q22.2 gain.A) Kaplan-Meier survival estimates of patient groups with and without gain of chromosome 11q22.1–q22.2; survival in months (x-axis) is plotted against the fraction of samples alive (y-axis). Interphase FISH analysis detecting the chromosome 11 centromere (red) and the 11q22.1–q22.2 region (green), B) A case without 11q22.1-q22.2 gain and C) A case of 11q22.1–q22.2 gain are shown.
Mentions: Loss of 11q23–q25 (P = 0.0001) and gain of 11q22.1–q22.2 (P = 0.009) were found as the strongest predictors of poor clinical outcome in terms of recurrence and survival (Table 4). Kaplan-Meier survival curves for loss of distal 11q and gain of 11q22.1-q22.2 are shown in Figures 3A and 4A. The chromosomal interval 11q23–q25 was subdivided by RAE into four non-overlapping intervals. The p-values for the four association tests were almost identical, but the subdivision suggests that there were multiple pertinent genes on 11q23–q25, at least one gene per subinterval.

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