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Discordant p53 gene mutations in primary head and neck cancers and corresponding second primary cancers of the upper aerodigestive tract.
Cancer Res 1993; 53(7):1676-83CR

Abstract

Patients with primary head and neck malignancies have a 3-7% yearly incidence of second primary cancers. It is thought that these second primary cancers arise independently following exposure to a common carcinogen by a process that has been called field cancerization. Since mutations in the p53 tumor suppressor gene represent a genetic alteration occurring during the evolution of premalignant lesions to malignancies of the upper aerodigestive tract, we analyzed mutations in the p53 gene of patients with cancer of the head and neck who developed second primary tumors of the upper aerodigestive tract epithelium to test the field cancerization hypothesis. DNA was extracted from primary head and neck cancers and second primary cancers of 31 patients. DNA from exons 5-8 of the p53 gene was analyzed by the single strand conformation polymorphism technique to identify the locations of the mutations in different regions of the gene. DNA from 6 patients was also sequenced by the chain termination method to confirm the presence of mutations and determine the base substitutions. Twenty-one of the 31 patients had 1 or more p53 mutations. In all 21 cases the genetic lesions were discordant such that the presence or location of the mutations in the initial primary cancer differed from those of the second and third primary cancers. In each of the five patients with mutations in both primary tumors, the mutations occurred in different regions of the p53 gene. Of the other 16 patients, 8 had a p53 mutation in the first primary but not the subsequent primary cancer and the other 8 had no mutation in the initial primary but did have a mutation in subsequent primary cancers. Sequencing confirmed the single strand conformation polymorphism analysis and showed that 73% of the mutations were transitions. The discordant p53 mutations in second primary cancers arising in patients with primary epithelial cancer of the upper aerodigestive tract suggest that these cancers arise as independent events. These observations provide the first demonstration of a molecular basis for field cancerization effects in cancers of the upper aerodigestive tract.

Authors+Show Affiliations

Department of Thoracic Surgery, University of Texas M.D. Anderson Cancer Center, Houston 77030.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8453641

Citation

Chung, K Y., et al. "Discordant P53 Gene Mutations in Primary Head and Neck Cancers and Corresponding Second Primary Cancers of the Upper Aerodigestive Tract." Cancer Research, vol. 53, no. 7, 1993, pp. 1676-83.
Chung KY, Mukhopadhyay T, Kim J, et al. Discordant p53 gene mutations in primary head and neck cancers and corresponding second primary cancers of the upper aerodigestive tract. Cancer Res. 1993;53(7):1676-83.
Chung, K. Y., Mukhopadhyay, T., Kim, J., Casson, A., Ro, J. Y., Goepfert, H., ... Roth, J. A. (1993). Discordant p53 gene mutations in primary head and neck cancers and corresponding second primary cancers of the upper aerodigestive tract. Cancer Research, 53(7), pp. 1676-83.
Chung KY, et al. Discordant P53 Gene Mutations in Primary Head and Neck Cancers and Corresponding Second Primary Cancers of the Upper Aerodigestive Tract. Cancer Res. 1993 Apr 1;53(7):1676-83. PubMed PMID: 8453641.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discordant p53 gene mutations in primary head and neck cancers and corresponding second primary cancers of the upper aerodigestive tract. AU - Chung,K Y, AU - Mukhopadhyay,T, AU - Kim,J, AU - Casson,A, AU - Ro,J Y, AU - Goepfert,H, AU - Hong,W K, AU - Roth,J A, PY - 1993/4/1/pubmed PY - 1993/4/1/medline PY - 1993/4/1/entrez SP - 1676 EP - 83 JF - Cancer research JO - Cancer Res. VL - 53 IS - 7 N2 - Patients with primary head and neck malignancies have a 3-7% yearly incidence of second primary cancers. It is thought that these second primary cancers arise independently following exposure to a common carcinogen by a process that has been called field cancerization. Since mutations in the p53 tumor suppressor gene represent a genetic alteration occurring during the evolution of premalignant lesions to malignancies of the upper aerodigestive tract, we analyzed mutations in the p53 gene of patients with cancer of the head and neck who developed second primary tumors of the upper aerodigestive tract epithelium to test the field cancerization hypothesis. DNA was extracted from primary head and neck cancers and second primary cancers of 31 patients. DNA from exons 5-8 of the p53 gene was analyzed by the single strand conformation polymorphism technique to identify the locations of the mutations in different regions of the gene. DNA from 6 patients was also sequenced by the chain termination method to confirm the presence of mutations and determine the base substitutions. Twenty-one of the 31 patients had 1 or more p53 mutations. In all 21 cases the genetic lesions were discordant such that the presence or location of the mutations in the initial primary cancer differed from those of the second and third primary cancers. In each of the five patients with mutations in both primary tumors, the mutations occurred in different regions of the p53 gene. Of the other 16 patients, 8 had a p53 mutation in the first primary but not the subsequent primary cancer and the other 8 had no mutation in the initial primary but did have a mutation in subsequent primary cancers. Sequencing confirmed the single strand conformation polymorphism analysis and showed that 73% of the mutations were transitions. The discordant p53 mutations in second primary cancers arising in patients with primary epithelial cancer of the upper aerodigestive tract suggest that these cancers arise as independent events. These observations provide the first demonstration of a molecular basis for field cancerization effects in cancers of the upper aerodigestive tract. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/8453641/Discordant_p53_gene_mutations_in_primary_head_and_neck_cancers_and_corresponding_second_primary_cancers_of_the_upper_aerodigestive_tract_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=8453641 DB - PRIME DP - Unbound Medicine ER -