Divergent routes to oral cancer. Export

@article{citeulike:1653262, abstract = {Most head and neck squamous cell carcinoma (HNSCC) patients present with late-stage cancers, which are difficult to treat. Therefore, early diagnosis of high-risk premalignant lesions and incipient cancers is important. HNSCC is currently perceived as a single progression mechanism, resulting in immortal invasive cancers. However, we have found that approximately 40\% of primary oral SCCs are mortal in culture, and these have a better prognosis. About 60\% of oral premalignancies (dysplasias) are also mortal. The mortal and immortal tumors are generated in vivo as judged by p53 mutations and loss of p16(INK4A) expression being found only in the original tumors from which the immortal cultures were derived. To investigate the relationships of dysplasias to SCCs, we did microarray analysis of primary cultures of 4 normal oral mucosa biopsies, 19 dysplasias, and 16 SCCs. Spectral clustering using the singular value decomposition and other bioinformatic techniques showed that development of mortal and immortal SCCs involves distinct transcriptional changes. Both SCC classes share most of the transcriptional changes found in their respective dysplasias but have additional changes. Moreover, high-risk dysplasias that subsequently progress to SCCs more closely resemble SCCs than nonprogressing dysplasias. This indicates for the first time that there are divergent mortal and immortal pathways for oral SCC development via intermediate dysplasias. We believe that this new information may lead to new ways of classifying HNSCC in relation to prognosis.}, address = {The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, UK.}, author = {Hunter, K. D. and Thurlow, J. K. and Fleming, J. and Drake, P. J. and Vass, J. K. and Kalna, G. and Higham, D. J. and Herzyk, P. and Macdonald, D. G. and Parkinson, E. K. and Harrison, P. R.}, citeulike-article-id = {1653262}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/0008-5472.CAN-06-0186}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16885335}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16885335}, day = {1}, doi = {10.1158/0008-5472.CAN-06-0186}, issn = {0008-5472}, journal = {Cancer Res}, keywords = {cancer, classification-prognosis, microarray, oral, scc}, month = {August}, number = {15}, pages = {7405--7413}, posted-at = {2007-09-13 23:40:59}, priority = {3}, title = {Divergent routes to oral cancer.}, url = {http://dx.doi.org/10.1158/0008-5472.CAN-06-0186}, volume = {66}, year = {2006} }

TY - JOUR ID - citeulike:1653262 L3 - citeulike-article-id:1653262 N2 - Most head and neck squamous cell carcinoma (HNSCC) patients present with late-stage cancers, which are difficult to treat. Therefore, early diagnosis of high-risk premalignant lesions and incipient cancers is important. HNSCC is currently perceived as a single progression mechanism, resulting in immortal invasive cancers. However, we have found that approximately 40% of primary oral SCCs are mortal in culture, and these have a better prognosis. About 60% of oral premalignancies (dysplasias) are also mortal. The mortal and immortal tumors are generated in vivo as judged by p53 mutations and loss of p16(INK4A) expression being found only in the original tumors from which the immortal cultures were derived. To investigate the relationships of dysplasias to SCCs, we did microarray analysis of primary cultures of 4 normal oral mucosa biopsies, 19 dysplasias, and 16 SCCs. Spectral clustering using the singular value decomposition and other bioinformatic techniques showed that development of mortal and immortal SCCs involves distinct transcriptional changes. Both SCC classes share most of the transcriptional changes found in their respective dysplasias but have additional changes. Moreover, high-risk dysplasias that subsequently progress to SCCs more closely resemble SCCs than nonprogressing dysplasias. This indicates for the first time that there are divergent mortal and immortal pathways for oral SCC development via intermediate dysplasias. We believe that this new information may lead to new ways of classifying HNSCC in relation to prognosis. IS - 15 JF - Cancer Res SN - 0008-5472 AD - The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, UK. EP - 7413 TI - Divergent routes to oral cancer. VL - 66 SP - 7405 KW - cancer KW - classification-prognosis KW - microarray KW - oral KW - scc AU - Hunter, KD AU - Thurlow, JK AU - Fleming, J AU - Drake, PJ AU - Vass, JK AU - Kalna, G AU - Higham, DJ AU - Herzyk, P AU - Macdonald, DG AU - Parkinson, EK AU - Harrison, PR PY - 2006/08/01/ UR - http://dx.doi.org/10.1158/0008-5472.CAN-06-0186 ER -