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Unique association of p53 mutations with undifferentiated but not with differentiated carcinomas of the thyroid gland
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ABSTRACTS
derstanding the natural neoplasia as well as the biologic markers induced rants careful study by chemoprevention.
history of intraepithelial importance of following by various agents. It warindividuals involved in
Chromosome
3p Deletions in Head and Neck Carcinomas: Statistical Ascertainment of Allelic Loss. F Latif, M Fivash, G Glenn, K Tory, ML Orcutt, K Hampsch, J Delisio, M Lerman, J Cowan, M Beckett, R Weichselbaum. Cancer Res
these with tumor stage and progression. This is a novel approach to the genetic study of head and neck squamous cell carcinoma.
Unique Association of ~53 Mutations With Undifferentiated But Not With Differentiated Carcinomas of the Thyroid Gland. T Ito, T Seyama, T Mizuno, N Tsuyama, T Hayashi, Y Hayashi, K Dohi, N Nakamura, M Akiyama. Cancer Res 52:
1369-1371,1992
52:1451-1456.1992 Head and neck tumors are known to be a heterogenous group of tumors that are widely disparate in clinical behavior. A lack of progress in the field of head and neck oncology reflects a lack of understanding of the molecular mechanisms associated with the origin and development of the neoplasms. In other tumors genetic alterations have been sought to clarify the process of neoplasia. It has been shown that in some cancers, deletions in a short arm of chromosome 3 are common, these include tumors of the lung and kidney. In contrast, few reports have described chromosomal losses in head and neck tumors. This report presents extensive allelotype analysis of the short arm of chromosome 3 using tumor cell lines from head and neck squamous carcinoma. The authors ascertain allelic loss by a novel statistical method and map the commonly deleted region. They show that the deleted portion of chromosome 3 probably lies in a large region that contains several putative tumor suppression genes implicated in multiple tumors of the lung, breast, and kidney. The dramatic loss of heterozygosity in this region suggests that tumor suppressor genes may be important in the pathogenesis of head and neck squamous cell carcinoma. The lines used in the study are derived from late stage 1 and early stage 2 patients at which point there were no discernable nodal metastases. Thus, genetic deletion may be most important in the initiation and early development of head and neck tumors. Further work is necessary in mapping the deleted sites with better precision and to correlate
Carcinogenesis is thought to consist of a multistep accumulation of adverse genetic and epigenetic events. These genetic events include activation of oncogenes or inactivation of tumor suppressor genes. Among the most studied tumor suppressor genes, ~53 is the best understood. Mutation in its structure has been shown to be associated with many types of tumors of the colon, lung, liver, and esophagus. The present study described the unique finding that ~53 mutations are uniquely associated with undifferentiated thyroid carcinomas but not with differentiated papillary adenocarcinoma. Ten cases of differentiated papillary adenocarcinoma, six cases of undifferentiated carcinoma, and one cell live from an undifferentiated carcinoma of the thyroid were investigated. Direct sequence analysis of ~53 gene were performed in 17 cases. No mutations could be detected in 10 differentiated papillary carcinomas whereas base change mutations were detected in 86% of the undifferentiated tumors. A base substitution found in the anaplastic cell line was a C:G to T:A transition. This base substitution pattern is similar to that found for most other cancers such as colon, breast, and lung. Undifferentiated thyroid carcinoma arises from preexisting differentiated tumors. The characteristics of slow growth of tumor cells with no ~53 mutations and rapid growth of cells with a high frequency of mutations suggests that this gene may be important in uncontrolled and undifferentiated tumors. This is an exciting preliminary report that implicates oncogene control of clinical behavior for thyroid tumors.
ABSTRACTS
derstanding the natural neoplasia as well as the biologic markers induced rants careful study by chemoprevention.
history of intraepithelial importance of following by various agents. It warindividuals involved in
Chromosome
3p Deletions in Head and Neck Carcinomas: Statistical Ascertainment of Allelic Loss. F Latif, M Fivash, G Glenn, K Tory, ML Orcutt, K Hampsch, J Delisio, M Lerman, J Cowan, M Beckett, R Weichselbaum. Cancer Res
these with tumor stage and progression. This is a novel approach to the genetic study of head and neck squamous cell carcinoma.
Unique Association of ~53 Mutations With Undifferentiated But Not With Differentiated Carcinomas of the Thyroid Gland. T Ito, T Seyama, T Mizuno, N Tsuyama, T Hayashi, Y Hayashi, K Dohi, N Nakamura, M Akiyama. Cancer Res 52:
1369-1371,1992
52:1451-1456.1992 Head and neck tumors are known to be a heterogenous group of tumors that are widely disparate in clinical behavior. A lack of progress in the field of head and neck oncology reflects a lack of understanding of the molecular mechanisms associated with the origin and development of the neoplasms. In other tumors genetic alterations have been sought to clarify the process of neoplasia. It has been shown that in some cancers, deletions in a short arm of chromosome 3 are common, these include tumors of the lung and kidney. In contrast, few reports have described chromosomal losses in head and neck tumors. This report presents extensive allelotype analysis of the short arm of chromosome 3 using tumor cell lines from head and neck squamous carcinoma. The authors ascertain allelic loss by a novel statistical method and map the commonly deleted region. They show that the deleted portion of chromosome 3 probably lies in a large region that contains several putative tumor suppression genes implicated in multiple tumors of the lung, breast, and kidney. The dramatic loss of heterozygosity in this region suggests that tumor suppressor genes may be important in the pathogenesis of head and neck squamous cell carcinoma. The lines used in the study are derived from late stage 1 and early stage 2 patients at which point there were no discernable nodal metastases. Thus, genetic deletion may be most important in the initiation and early development of head and neck tumors. Further work is necessary in mapping the deleted sites with better precision and to correlate
Carcinogenesis is thought to consist of a multistep accumulation of adverse genetic and epigenetic events. These genetic events include activation of oncogenes or inactivation of tumor suppressor genes. Among the most studied tumor suppressor genes, ~53 is the best understood. Mutation in its structure has been shown to be associated with many types of tumors of the colon, lung, liver, and esophagus. The present study described the unique finding that ~53 mutations are uniquely associated with undifferentiated thyroid carcinomas but not with differentiated papillary adenocarcinoma. Ten cases of differentiated papillary adenocarcinoma, six cases of undifferentiated carcinoma, and one cell live from an undifferentiated carcinoma of the thyroid were investigated. Direct sequence analysis of ~53 gene were performed in 17 cases. No mutations could be detected in 10 differentiated papillary carcinomas whereas base change mutations were detected in 86% of the undifferentiated tumors. A base substitution found in the anaplastic cell line was a C:G to T:A transition. This base substitution pattern is similar to that found for most other cancers such as colon, breast, and lung. Undifferentiated thyroid carcinoma arises from preexisting differentiated tumors. The characteristics of slow growth of tumor cells with no ~53 mutations and rapid growth of cells with a high frequency of mutations suggests that this gene may be important in uncontrolled and undifferentiated tumors. This is an exciting preliminary report that implicates oncogene control of clinical behavior for thyroid tumors.