DNA sequence analysis of exons 2 through 11 and immunohistochemical staining are required to detect all known p53 alterations in human malignancies

Graham Casey, Martha E. Lopez, Juan Carlos Ramos, Sarah J. Plummer, M. Jane Arboleda, Michael Shaughnessy, Beth Karlan, Dennis J. Slamon

Research output: Contribution to journalArticle

212 Citations (Scopus)

Abstract

p53 mutations are the most common genetic alterations found in human malignancies. However current estimates of p53 alterations in cancers may be inaccurate because there is evidence that current approaches do not detect all p53 alterations. In this study we determine the status of the p53 gene by complete DNA sequencing of exons 2 through 11 as well as immunohistochemical staining in cohorts of primary human breast, ovarian and non small cell lung cancer. Overall, 24 of 93 (26%) breast cancers, 62 of 108 (57%) ovarian cancers and 88 of 154 (57%) non small cell lung cancers contained DNA sequence mutations, whereas positive immunohistochemical staining was detected in 15 of 64 (23%) breast, 35 of 94 (37%) ovarian, and 63 of 137 (46%) lung cancers. Of those tumors that contained mutations, the mutation occurred outside the 'hot-spot' region in 19% of breast, 18% of ovarian and 17% of lung tumors, indicating that a substantial number of mutations remain undetected in studies that are restricted to exons 5 through 9. We observed a high concordance between the presence of p53 missense mutations and positive immunohistochemical staining, but a poor concordance between other types of mutations and staining in all three types of malignancies. We conclude that a combination of DNA sequence analysis of exons 2 through 11 and immunohistochemical staining are required to detect all known alterations in the p53 gene in human malignancies.

Original languageEnglish
Pages (from-to)1971-1981
Number of pages11
JournalOncogene
Volume13
Issue number9
StatePublished - Dec 9 1996
Externally publishedYes

Fingerprint

DNA Sequence Analysis
Exons
Staining and Labeling
Mutation
Neoplasms
Breast
p53 Genes
Non-Small Cell Lung Carcinoma
Missense Mutation
Ovarian Neoplasms
Lung Neoplasms
Breast Neoplasms
Lung

Keywords

  • Breast cancer
  • Immunohistochemical
  • Lung cancer
  • Mutations
  • Ovarian cancer
  • p53 tumor suppressor gene
  • Staining

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Casey, G., Lopez, M. E., Carlos Ramos, J., Plummer, S. J., Arboleda, M. J., Shaughnessy, M., ... Slamon, D. J. (1996). DNA sequence analysis of exons 2 through 11 and immunohistochemical staining are required to detect all known p53 alterations in human malignancies. Oncogene, 13(9), 1971-1981.

DNA sequence analysis of exons 2 through 11 and immunohistochemical staining are required to detect all known p53 alterations in human malignancies. / Casey, Graham; Lopez, Martha E.; Carlos Ramos, Juan; Plummer, Sarah J.; Arboleda, M. Jane; Shaughnessy, Michael; Karlan, Beth; Slamon, Dennis J.

In: Oncogene, Vol. 13, No. 9, 09.12.1996, p. 1971-1981.

Research output: Contribution to journalArticle

Casey, G, Lopez, ME, Carlos Ramos, J, Plummer, SJ, Arboleda, MJ, Shaughnessy, M, Karlan, B & Slamon, DJ 1996, 'DNA sequence analysis of exons 2 through 11 and immunohistochemical staining are required to detect all known p53 alterations in human malignancies', Oncogene, vol. 13, no. 9, pp. 1971-1981.
Casey, Graham ; Lopez, Martha E. ; Carlos Ramos, Juan ; Plummer, Sarah J. ; Arboleda, M. Jane ; Shaughnessy, Michael ; Karlan, Beth ; Slamon, Dennis J. / DNA sequence analysis of exons 2 through 11 and immunohistochemical staining are required to detect all known p53 alterations in human malignancies. In: Oncogene. 1996 ; Vol. 13, No. 9. pp. 1971-1981.
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