Detection of somatic TP53 mutations in tampons of patients with high-grade serous ovarian cancer

Britt K. Erickson, Isaac Kinde, Zachary C. Dobbin, Yuxuan Wang, Jovana Y. Martin, Ronald D. Alvarez, Michael G. Conner, Warner K. Huh, Richard S Roden, Kenneth W Kinzler, Nickolas Papadopoulos, Bert Vogelstein, Luis A. Diaz, Charles N. Landen

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To investigate whether tumor cells could be detected in the vagina of women with serous ovarian cancer through TP53 analysis of DNA samples collected by placement of a vaginal tampon.

METHODS: Women undergoing surgery for a pelvic mass were identified in the gynecologic oncology clinic. They placed a vaginal tampon before surgery, which was removed in the operating room. Cells were isolated and DNA was extracted from both the cells trapped within the tampon and the primary tumor. In patients with serous carcinoma, the DNA was interrogated for the presence of TP53 mutations using a method capable of detecting rare mutant alleles in a mixture of mutant and wild-type DNA.

RESULTS: Thirty-three patients were enrolled. Eight patients with advanced serous ovarian cancer were included for analysis. Three had a prior tubal ligation. TP53 mutations were identified in all eight tumor samples. Analysis of the DNA from the tampons revealed mutations in three of the five patients with intact tubes (sensitivity 60%) and in none of the three patients with tubal ligation. In all three participants with mutation detected in the tampon specimen, the tumor and the vaginal DNA harbored the exact same TP53 mutation. The fraction of DNA derived from exfoliated tumor cells ranged from 0.01% to 0.07%.

CONCLUSION: In this pilot study, DNA derived from tumor was detected in the vaginas of 60% of patients with ovarian cancer with intact fallopian tubes. With further development, this approach may hold promise for the early detection of this deadly disease.

Original languageEnglish (US)
Pages (from-to)881-885
Number of pages5
JournalObstetrics and Gynecology
Volume124
Issue number5
DOIs
StatePublished - Nov 1 2014

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Ovarian Neoplasms
Mutation
DNA
Menstrual Hygiene Products
Tubal Sterilization
Neoplasms
Vagina
Fallopian Tubes
Operating Rooms
Early Diagnosis
Alleles
Carcinoma

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Erickson, B. K., Kinde, I., Dobbin, Z. C., Wang, Y., Martin, J. Y., Alvarez, R. D., ... Landen, C. N. (2014). Detection of somatic TP53 mutations in tampons of patients with high-grade serous ovarian cancer. Obstetrics and Gynecology, 124(5), 881-885. https://doi.org/10.1097/AOG.0000000000000484

Detection of somatic TP53 mutations in tampons of patients with high-grade serous ovarian cancer. / Erickson, Britt K.; Kinde, Isaac; Dobbin, Zachary C.; Wang, Yuxuan; Martin, Jovana Y.; Alvarez, Ronald D.; Conner, Michael G.; Huh, Warner K.; Roden, Richard S; Kinzler, Kenneth W; Papadopoulos, Nickolas; Vogelstein, Bert; Diaz, Luis A.; Landen, Charles N.

In: Obstetrics and Gynecology, Vol. 124, No. 5, 01.11.2014, p. 881-885.

Research output: Contribution to journalArticle

Erickson, BK, Kinde, I, Dobbin, ZC, Wang, Y, Martin, JY, Alvarez, RD, Conner, MG, Huh, WK, Roden, RS, Kinzler, KW, Papadopoulos, N, Vogelstein, B, Diaz, LA & Landen, CN 2014, 'Detection of somatic TP53 mutations in tampons of patients with high-grade serous ovarian cancer', Obstetrics and Gynecology, vol. 124, no. 5, pp. 881-885. https://doi.org/10.1097/AOG.0000000000000484
Erickson, Britt K. ; Kinde, Isaac ; Dobbin, Zachary C. ; Wang, Yuxuan ; Martin, Jovana Y. ; Alvarez, Ronald D. ; Conner, Michael G. ; Huh, Warner K. ; Roden, Richard S ; Kinzler, Kenneth W ; Papadopoulos, Nickolas ; Vogelstein, Bert ; Diaz, Luis A. ; Landen, Charles N. / Detection of somatic TP53 mutations in tampons of patients with high-grade serous ovarian cancer. In: Obstetrics and Gynecology. 2014 ; Vol. 124, No. 5. pp. 881-885.
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abstract = "OBJECTIVE: To investigate whether tumor cells could be detected in the vagina of women with serous ovarian cancer through TP53 analysis of DNA samples collected by placement of a vaginal tampon.METHODS: Women undergoing surgery for a pelvic mass were identified in the gynecologic oncology clinic. They placed a vaginal tampon before surgery, which was removed in the operating room. Cells were isolated and DNA was extracted from both the cells trapped within the tampon and the primary tumor. In patients with serous carcinoma, the DNA was interrogated for the presence of TP53 mutations using a method capable of detecting rare mutant alleles in a mixture of mutant and wild-type DNA.RESULTS: Thirty-three patients were enrolled. Eight patients with advanced serous ovarian cancer were included for analysis. Three had a prior tubal ligation. TP53 mutations were identified in all eight tumor samples. Analysis of the DNA from the tampons revealed mutations in three of the five patients with intact tubes (sensitivity 60{\%}) and in none of the three patients with tubal ligation. In all three participants with mutation detected in the tampon specimen, the tumor and the vaginal DNA harbored the exact same TP53 mutation. The fraction of DNA derived from exfoliated tumor cells ranged from 0.01{\%} to 0.07{\%}.CONCLUSION: In this pilot study, DNA derived from tumor was detected in the vaginas of 60{\%} of patients with ovarian cancer with intact fallopian tubes. With further development, this approach may hold promise for the early detection of this deadly disease.",
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AU - Kinde, Isaac

AU - Dobbin, Zachary C.

AU - Wang, Yuxuan

AU - Martin, Jovana Y.

AU - Alvarez, Ronald D.

AU - Conner, Michael G.

AU - Huh, Warner K.

AU - Roden, Richard S

AU - Kinzler, Kenneth W

AU - Papadopoulos, Nickolas

AU - Vogelstein, Bert

AU - Diaz, Luis A.

AU - Landen, Charles N.

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