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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)7024-7034
Number of pages11
JournalClinical Cancer Research
Volume17
Issue number22
DOIs
StatePublished - Nov 15 2011

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Genomic Instability
Mouth Neoplasms
Neoplasm Metastasis
Squamous Cell Carcinoma
Chromosomal Instability
Neoplasms
Comparative Genomic Hybridization
Chromosome Aberrations
Methylation
Research Design
Neck
Biomarkers
Lymph Nodes
Recurrence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Two distinct routes to oral cancer differing in genome instability and risk for cervical node metastasis. / Bhattacharya, Aditi; Roy, Ritu; Snijders, Antoine M.; Hamilton, Gregory; Paquette, Jesse; Tokuyasu, Taku; Bengtsson, Henrik; Jordan, Richard C K; Olshen, Adam B.; Pinkel, Daniel; Schmidt, Brian; Albertson, Donna.

In: Clinical Cancer Research, Vol. 17, No. 22, 15.11.2011, p. 7024-7034.

Research output: Contribution to journalArticle

Bhattacharya, A, Roy, R, Snijders, AM, Hamilton, G, Paquette, J, Tokuyasu, T, Bengtsson, H, Jordan, RCK, Olshen, AB, Pinkel, D, Schmidt, B & Albertson, D 2011, 'Two distinct routes to oral cancer differing in genome instability and risk for cervical node metastasis', Clinical Cancer Research, vol. 17, no. 22, pp. 7024-7034. https://doi.org/10.1158/1078-0432.CCR-11-1944
Bhattacharya, Aditi ; Roy, Ritu ; Snijders, Antoine M. ; Hamilton, Gregory ; Paquette, Jesse ; Tokuyasu, Taku ; Bengtsson, Henrik ; Jordan, Richard C K ; Olshen, Adam B. ; Pinkel, Daniel ; Schmidt, Brian ; Albertson, Donna. / Two distinct routes to oral cancer differing in genome instability and risk for cervical node metastasis. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 22. pp. 7024-7034.
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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.",
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AU - Paquette, Jesse

AU - Tokuyasu, Taku

AU - Bengtsson, Henrik

AU - Jordan, Richard C K

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AU - Pinkel, Daniel

AU - Schmidt, Brian

AU - Albertson, Donna

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