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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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Array CGH based identification of 9p23-p24.1 loss encompassing putative tumor suppressor gene PTPRD.
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pone-0017250-g002: Array CGH based identification of 9p23-p24.1 loss encompassing putative tumor suppressor gene PTPRD.

Mentions: The most frequently occurring losses were identified on chromosomal regions 3p (62%), 5q (37%), 8p (83%), 9p (28%), 10p (35%), 11q (20%), 13p13 (32%), 18q (30%), and 19p12 (13%) as represented in Table S2. Focal regions of loss included 1q24.2 (harboring the candidate gene NME7), 2q21.2 (NCKAP5), 3p14.2 (PTPRG), 3p25.2–p26.3 (CHL1, GRM7, RAD18, SRGAP3), 4q35.2 (MTNR1A, FAT1), 6p21.3 (HLA-DRA, HLA-DRB5, HLA-DRB6, HLA-DRB1), 8p23.1 (CSMD1), 8p11.2 (ADAM5P, ADAM3A), 9p21 (MTAP, C9orf53, CDKN2A, CDKN2BAS, CDKN2B) 9p23-p24.3 (PTPRD), 17p13.3 (RPH3AL, MGC70870), and 22q13.1 (APOBEC3A, APOBEC3B) and is presented in Table S2. The previously unreported focal loss of 9p23-p24.1 (PTPRD) in oral cancer is shown in Figure 2.


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)

Array CGH based identification of 9p23-p24.1 loss encompassing putative tumor suppressor gene PTPRD.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0017250-g002: Array CGH based identification of 9p23-p24.1 loss encompassing putative tumor suppressor gene PTPRD.
Mentions: The most frequently occurring losses were identified on chromosomal regions 3p (62%), 5q (37%), 8p (83%), 9p (28%), 10p (35%), 11q (20%), 13p13 (32%), 18q (30%), and 19p12 (13%) as represented in Table S2. Focal regions of loss included 1q24.2 (harboring the candidate gene NME7), 2q21.2 (NCKAP5), 3p14.2 (PTPRG), 3p25.2–p26.3 (CHL1, GRM7, RAD18, SRGAP3), 4q35.2 (MTNR1A, FAT1), 6p21.3 (HLA-DRA, HLA-DRB5, HLA-DRB6, HLA-DRB1), 8p23.1 (CSMD1), 8p11.2 (ADAM5P, ADAM3A), 9p21 (MTAP, C9orf53, CDKN2A, CDKN2BAS, CDKN2B) 9p23-p24.3 (PTPRD), 17p13.3 (RPH3AL, MGC70870), and 22q13.1 (APOBEC3A, APOBEC3B) and is presented in Table S2. The previously unreported focal loss of 9p23-p24.1 (PTPRD) in oral cancer is shown in Figure 2.

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