Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Nov 15;17(22):7024-34.
doi: 10.1158/1078-0432.CCR-11-1944. Epub 2011 Nov 8.

Two distinct routes to oral cancer differing in genome instability and risk for cervical node metastasis

Aditi Bhattacharya  1 , Ritu Roy, Antoine M Snijders, Gregory Hamilton, Jesse Paquette, Taku Tokuyasu, Henrik Bengtsson, Richard C K Jordan, Adam B Olshen, Daniel Pinkel, Brian L Schmidt, Donna G Albertson
Affiliations

Two distinct routes to oral cancer differing in genome instability and risk for cervical node metastasis

Aditi Bhattacharya et al. Clin Cancer Res. .

Abstract

Purpose: Problems in management of oral cancers or precancers include identification of patients at risk for metastasis, tumor recurrence, and second primary tumors or risk for progression of precancers (dysplasia) to cancer. Thus, the objective of this study was to clarify the role of genomic aberrations in oral cancer progression and metastasis.

Experimental design: The spectrum of copy number alterations in oral dysplasia and squamous cell carcinomas (SCC) was determined by array comparative genomic hybridization. Associations with clinical characteristics were studied and results confirmed in an independent cohort.

Results: The presence of one or more of the chromosomal aberrations +3q24-qter, -8pter-p23.1, +8q12-q24.2, and +20 distinguishes a major subgroup (70%-80% of lesions, termed 3q8pq20 subtype) from the remainder (20%-30% of lesions, non-3q8pq20). The 3q8pq20 subtype is associated with chromosomal instability and differential methylation in the most chromosomally unstable tumors. The two subtypes differ significantly in clinical outcome with risk for cervical (neck) lymph node metastasis almost exclusively associated with the 3q8pq20 subtype in two independent oral SCC cohorts.

Conclusions: Two subtypes of oral lesions indicative of at least two pathways for oral cancer development were distinguished that differ in chromosomal instability and risk for metastasis, suggesting that +3q,-8p, +8q, and +20 constitute a biomarker with clinical utility for identifying patients at risk for metastasis. Moreover, although increased numbers of genomic alterations can be harbingers of progression to cancer, dysplastic lesions lacking copy number changes cannot be considered benign as they are potential precursors to non-3q8pq20 locally invasive, yet not metastatic oral SCC.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Copy number aberrations involving 3q, 8p, 8q and chromosome 20 are frequent in oral dysplasia and occur at similar frequency in oral SCC
(A and B) Frequency of copy number aberrations shown in genome order for each clone on the array in 29 oral dysplasia samples with no known association with cancer (A) and oral SCC cohort#1 (B). We indicate gains by red bars ranging in frequency from 0 to 0.6 and, losses by blue bars ranging from 0 to -0.6. Chromosome boundaries are indicated by vertical lines. The frequency scales are truncated at 0.6 for both gains and losses since no frequency exceeded this bound. (C and D) Hierarchical clustering based on DNA copy number profiles of 29 oral dysplasia samples with no known association with cancer (C) and oral SCC cohort#1 (D). We represented the individual clones on the array as rows, ordered by chromosome and genome position. The vertical band on the left side of the heatmap indicates the genome positions of the clones on chromosomes. Clones on the p-arm are indicated either in light blue or yellow and clones on the q-arm in dark blue or green. We show acrocentric chromosomes in green or dark blue. Columns represent individual samples. A gain or a loss at a particular locus for a particular sample is indicated by red and blue, respectively and focal amplifications by yellow dots. The bands across the top of the heatmap indicate characteristics of each case: dysplasia grade (mild, light blue; moderate, dark blue; severe, purple), TP53 mutation status (TP53 mutant, dark blue; no detected mutation, light blue; TP53 status unknown, white) and the 3q8pq20 status (3q8pq20, dark blue; non-3q8pq20, light blue). (E) Frequencies of gains of 3q, 8q, 20 and loss of 8p in oral dysplasia and SCC normalized to the total number of aberrations at these loci in each cohort. (F) Frequency of 3q8pq20 and non-3q8pq20 cases in oral dysplasia and SCC.
Figure 2
Figure 2. Distribution of low level gains and losses among 3q8pq20 and non-3q8pq20 oral SCC cases
Hierarchical clustering based on DNA copy number profiles of non-3q8pq20 (left) and 3q8pq20 (right) cases in SCC cohort#1 (A) and cohort#2 (B) as in Figure 1C and D. The enhanced genomic instability associated with the 3q8pq20 subtype results in recurrent aberrations being more frequent in 3q8pq20 tumors (e.g., mean number of recurrent aberrations occurring at ≥15% frequency in cohort#1 = 4.53, range 1-13 compared to non-3q8pq20 tumors with mean = 0.79, range 0-7). The bands across the top of the heatmap show TP53 status as in Figure 1 or nodal status (N+ = dark blue, N0 = light blue).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin. 1999;49:33–64, 1. - PubMed
    1. Silverman SJ. Epidemiology. D.C. Decker Inc; 1998.
    1. Shiboski CH, Schmidt BL, Jordan RC. Tongue and tonsil carcinoma: increasing trends in the U.S. population ages 20-44 years. Cancer. 2005;103:1843–9. - PubMed
    1. Schmidt BL, Dierks EJ, Homer L, Potter B. Tobacco smoking history and presentation of oral squamous cell carcinoma. J Oral Maxillofac Surg. 2004;62:1055–8. - PubMed
    1. Gillison ML. Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity. Semin Oncol. 2004;31:744–54. - PubMed

Publication types