Different chromosomal imbalances in metastasized and nonmetastasized tongue carcinomas identified by comparative genomic hybridization

Hannen, E.J.M.; Macville, Merryn; Wienk, S.; Slootweg, Pieter J.; Manni, Johannes J.; Hanselaar, A. G. J. M.; Wilde, P.C.M. de

doi:10.1016/j.oraloncology.2003.09.011

Cited by 8 publications

(6 citation statements)

References 25 publications

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“…These results suggest that one or more gene(s) in 15q21.3 are important for the capacity to metastasize in head and neck squamous cell carcinomas. Losses of the long arm of chromosome 15 have already been described to correlate with metastasizing head and neck carcinomas 8 (including metastasizing tongue carcinomas 12 ) underling the value of our results. In contrast, alterations in the regions 2 and 3 were predominantly found in metastases but only in few primary tumors with lymph node status pN40.…”

Section: Discussionsupporting

confidence: 81%

“…4,[8][9][10][11][12][13] In this study, three regions of aberrations on the long arm of chromosome 15 could be identified in head and neck primary tumors and metastases. The most frequently affected region 1 stretches between D15S106 and D15S1029 in 15q21.3, region 2 lies more proximal in 15q13.3-q14 between D15S144 and D15S1040, and region 3 more distal in 15q26.2-q26.3 between D15S130 and D15S985.…”

Section: Discussionmentioning

confidence: 99%

“…Deletions or structural rearrangements in 15q as well as gains of genetic material from 15q have been described in a variety of studies in oral and esophageal squamous cell carcinomas. [8][9][10][11][12][13][14][15] Furthermore, a genome-wide study with microsatellite markers in head and neck squamous cell carcinomas demonstrated new hot spots for allelic losses in 15q, especially in 15q21. 4 Here, we studied 40 microsatellite markers from the long arm of chromosome 15 in 63 oral, pharyngeal, and laryngeal primary tumors and 38 lymph node metastases by multiplex PCRs.…”

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confidence: 99%

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Loss of heterozygosity at 15q21.3 correlates with occurrence of metastases in head and neck cancer

Poetsch

Kleist

2006

Modern Pathology

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Deletions on the long arm of chromosome 15 suggesting the presence of potential tumor suppressor genes have been found in several tumors including carcinomas of the colorectum, urinary bladder, breast, lung, and head and neck. Here, we analyzed allelic imbalance on chromosome 15q in head and neck carcinomas and corresponding lymph node metastases to define common regions of aberrations with potential involvement in development and progression of these tumors. We studied a panel of 40 polymorphic microsatellite markers, spanning 15q13-15q26, in 63 head and neck carcinomas and 38 lymph node metastases. Loss of heterozygosity (LOH) could be demonstrated in 34 primary tumors (54%) and 35 metastases (92%). Aberration mapping defined three minimum regions of aberrations: a region between the markers D15S106 and D15S1029 in 15q21.3 (estimated as 3.9 Mb; region 1) was affected in the majority of tumors, whereas two other regions between D15S144 and D15S1040 in 15q13.3-14 (estimated as 2.4 Mb; region 2) and between D15S130 and D15S985 in 15q26.2-26.3 (estimated as 4.7 Mb; region 3) were less often involved. Allelic loss in region 1 correlated with T stages (P ¼ 0.0029) and metastatic potential (P ¼ 0.0018). LOH in regions 2 and 3 occurred predominantly in metastases (P ¼ 0.0129 and P ¼ 0.0013, respectively). No correlation with grading, localization, or clinical outcome could be established for any of the affected regions. Our data hint at aberrations in 15q21.3 as a possible important characteristic for head and neck squamous cell carcinomas with risk of progression.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Loss of heterozygosity at 15q21.3 correlates with occurrence of metastases in head and neck cancer

Poetsch

Kleist

2006

Modern Pathology

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“…To further assess some of the CNAs detected by CGH on chromosome arm 11q, we performed FISH on 32 samples and evaluated sub-band 11q13 which has been reported previously to be frequently gained (11, 12, 14). The results obtained from tumor samples were compared to three normal oral mucosa samples.…”

Section: Resultsmentioning

confidence: 99%

Clinicopathological and prognostic implications of genetic alterations in oral cancers

et al. 2011

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This study evaluated the clinicopathological and prognostic implications of genetic alterations characterizing oral squamous cell carcinoma(OSCC). Comparative genomic hybridization(CGH) was used to identify chromosomal alterations present in primary OSCCs obtained from 97 pateints. In this population, tobacco use was a significant risk factor for OSCC. By contrast, all 97 of our samples are negative for human papillomavirus (HPV) DNA integration, which is another known risk factor for OSCC in certain populations. Results of the Fisher’s exact test followed by Benjamini-Hochberg correction for multiple testing, showed a correlation of 7p gain and 8p loss with node-positive OSCC (p≤0.04 for both genetic alterations) and association of 11q13 gain with high-grade OSCC (p≤0.05). Univariate Cox-proportional hazard models, also corrected for multiple testing, showed significant association of 11q13 gain and 18q loss with decreased survival (p≤0.05). These findings were supported by multivariate analysis which revealed that 11q13 gain and 18q loss together serve as a strong bivariate predictor of poor prognosis. In conclusion, our study has identified genetic alterations that correlate significantly with nodal status, grade, and poor survival status of OSCC. These potential biomarkers may aid the current TNM system for better prediction of clinical outcome.

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“…Their tumors were all large lesions with local invasion and extensive lymph node involvement. The first region from chromosome 7 (gain 8) overlaps with the 7q21 chromosomal region previously reported to be present in additional copies in head and neck cancer [ 33 ]. Although it contains many interesting genes which are continuously studied with respect to their role in cancer development in an ever increasing body of research, a well-established biomarker has not emerged so far.…”

Section: Discussionmentioning

confidence: 99%

Identification of genomic copy number variations associated with specific clinical features of head and neck cancer

et al. 2018

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BackgroundCopy number variations (CNSs) of large genomic regions are an important mechanism implicated in the development of head and neck cancer, however, for most changes their exact role is not well understood. The aim of this study was to find possible associations between gains/losses of genomic regions and clinically distinct subgroups of head and neck cancer patients.ResultsArray comparative genomic hybridization (aCGH) analysis was performed on DNA samples in 64 patients with cancer in oral cavity, oropharynx or hypopharynx. Overlapping genomic regions created from gains and losses were used for statistical analysis. Following regions were overrepresented: in tumors with stage I or II a gain of 2.98 Mb on 6p21.2-p11 and a gain of 7.4 Mb on 8q11.1-q11.23; in tumors with grade I histology a gain of 1.1 Mb on 8q24.13, a loss of a large part of p arm of chromosome 3, a loss of a 1.24 Mb on 6q14.3, and a loss of terminal 32 Mb region of 8p23.3; in cases with affected lymph nodes a gain of 0.75 Mb on 3q24, and a gain of 0.9 Mb on 3q26.32-q26.33; in cases with unaffected lymph nodes a gain of 1.1 Mb on 8q23.3, in patients not treated with surgery a gain of 12.2 Mb on 7q21.3-q22.3 and a gain of 0.33 Mb on 20q11.22.ConclusionsOur study identified several genomic regions of interest which appear to be associated with various clinically distinct subgroups of head and neck cancer. They represent a potentially important source of biomarkers useful for the clinical management of head and neck cancer. In particular, the PIK3CA and AGTR1 genes could be singled out to predict the lymph node involvement.

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Different chromosomal imbalances in metastasized and nonmetastasized tongue carcinomas identified by comparative genomic hybridization

Cited by 8 publications

References 25 publications

Loss of heterozygosity at 15q21.3 correlates with occurrence of metastases in head and neck cancer

Loss of heterozygosity at 15q21.3 correlates with occurrence of metastases in head and neck cancer

Clinicopathological and prognostic implications of genetic alterations in oral cancers

Identification of genomic copy number variations associated with specific clinical features of head and neck cancer

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