DNA methylation in anal intraepithelial lesions and anal squamous cell carcinoma

Jun Zhang, Giro R. Martins, Zoya B. Pansier, Kristina L. Roemer, Erik A. Kincaid, Karen S. Gustafson, Daniel F. Heitjan, Douglas P. Clark

Research output: Contribution to journalArticle

Abstract

Purpose: Anal intraepithelial neoplasia is associated with human papillomavirus infection and may progress to invasive squamous cell carcinoma (SCC), which is increasing in immunocompromised patients. We hypothesize that anal intraepithelial neoplasia is associated with abnormal DNA methylation and that detection of these events may be used to improve screening programs. Experimental Design: Seventy-six patients were identified who underwent anal cytology screening and subsequent biopsy at our institution between 1999 and 2004. The specimens from these patients included 184 anal biopsies [normal, n = 57; low-grade squamous intraepithelial lesion (LSIL), n = 74; high-grade squamous intraepithelial lesion (HSIL), n = 41; and invasive SCC, n = 12] and 37 residual liquid-based anal cytology specimens (normal, n = 11; LSIL, n = 12; HSIL, n = 14). The methylation status of the following genes was determined for each biopsy and cytology sample using real-time methylation-specific PCR: HIC1, RASSF1, RARB, CDKN2A, p14, TP73, APC, MLH1, MGMT, DAPK1, and IGSF4. Results: Methylation-specific PCR analysis of biopsy samples revealed that DNA methylation was more common in SCC and HSIL than LSIL and normal mucosa. Specifically, methylation of IGSF4 and DAPK1 was prevalent in SCC (75% and 75% of cases, respectively) and HSIL (59% and 71%, respectively) but was absent in LSIL and normal biopsy samples. Methylation profiles of cytologic samples were similar to those found in the biopsy samples. Conclusions: Aberrant DNA methylation is a frequent event in anal HSIL and SCC. Methylation of IGSF4 and DAPK1 is specific for HSIL and SCC, and may serve as a useful molecular biomarker.

Original languageEnglish (US)
Pages (from-to)6544-6549
Number of pages6
JournalClinical Cancer Research
Volume11
Issue number18
DOIs
StatePublished - Sep 15 2005

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DNA Methylation
Squamous Cell Carcinoma
Methylation
Biopsy
Cell Biology
Squamous Intraepithelial Lesions of the Cervix
Polymerase Chain Reaction
Papillomavirus Infections
Immunocompromised Host
Neoplasms
Mucous Membrane
Research Design
Biomarkers

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Zhang, J., Martins, G. R., Pansier, Z. B., Roemer, K. L., Kincaid, E. A., Gustafson, K. S., ... Clark, D. P. (2005). DNA methylation in anal intraepithelial lesions and anal squamous cell carcinoma. Clinical Cancer Research, 11(18), 6544-6549. https://doi.org/10.1158/1078-0432.CCR-05-0374

DNA methylation in anal intraepithelial lesions and anal squamous cell carcinoma. / Zhang, Jun; Martins, Giro R.; Pansier, Zoya B.; Roemer, Kristina L.; Kincaid, Erik A.; Gustafson, Karen S.; Heitjan, Daniel F.; Clark, Douglas P.

In: Clinical Cancer Research, Vol. 11, No. 18, 15.09.2005, p. 6544-6549.

Research output: Contribution to journalArticle

Zhang, J, Martins, GR, Pansier, ZB, Roemer, KL, Kincaid, EA, Gustafson, KS, Heitjan, DF & Clark, DP 2005, 'DNA methylation in anal intraepithelial lesions and anal squamous cell carcinoma', Clinical Cancer Research, vol. 11, no. 18, pp. 6544-6549. https://doi.org/10.1158/1078-0432.CCR-05-0374
Zhang J, Martins GR, Pansier ZB, Roemer KL, Kincaid EA, Gustafson KS et al. DNA methylation in anal intraepithelial lesions and anal squamous cell carcinoma. Clinical Cancer Research. 2005 Sep 15;11(18):6544-6549. https://doi.org/10.1158/1078-0432.CCR-05-0374
Zhang, Jun ; Martins, Giro R. ; Pansier, Zoya B. ; Roemer, Kristina L. ; Kincaid, Erik A. ; Gustafson, Karen S. ; Heitjan, Daniel F. ; Clark, Douglas P. / DNA methylation in anal intraepithelial lesions and anal squamous cell carcinoma. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 18. pp. 6544-6549.
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abstract = "Purpose: Anal intraepithelial neoplasia is associated with human papillomavirus infection and may progress to invasive squamous cell carcinoma (SCC), which is increasing in immunocompromised patients. We hypothesize that anal intraepithelial neoplasia is associated with abnormal DNA methylation and that detection of these events may be used to improve screening programs. Experimental Design: Seventy-six patients were identified who underwent anal cytology screening and subsequent biopsy at our institution between 1999 and 2004. The specimens from these patients included 184 anal biopsies [normal, n = 57; low-grade squamous intraepithelial lesion (LSIL), n = 74; high-grade squamous intraepithelial lesion (HSIL), n = 41; and invasive SCC, n = 12] and 37 residual liquid-based anal cytology specimens (normal, n = 11; LSIL, n = 12; HSIL, n = 14). The methylation status of the following genes was determined for each biopsy and cytology sample using real-time methylation-specific PCR: HIC1, RASSF1, RARB, CDKN2A, p14, TP73, APC, MLH1, MGMT, DAPK1, and IGSF4. Results: Methylation-specific PCR analysis of biopsy samples revealed that DNA methylation was more common in SCC and HSIL than LSIL and normal mucosa. Specifically, methylation of IGSF4 and DAPK1 was prevalent in SCC (75{\%} and 75{\%} of cases, respectively) and HSIL (59{\%} and 71{\%}, respectively) but was absent in LSIL and normal biopsy samples. Methylation profiles of cytologic samples were similar to those found in the biopsy samples. Conclusions: Aberrant DNA methylation is a frequent event in anal HSIL and SCC. Methylation of IGSF4 and DAPK1 is specific for HSIL and SCC, and may serve as a useful molecular biomarker.",
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AU - Martins, Giro R.

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AU - Kincaid, Erik A.

AU - Gustafson, Karen S.

AU - Heitjan, Daniel F.

AU - Clark, Douglas P.

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AB - Purpose: Anal intraepithelial neoplasia is associated with human papillomavirus infection and may progress to invasive squamous cell carcinoma (SCC), which is increasing in immunocompromised patients. We hypothesize that anal intraepithelial neoplasia is associated with abnormal DNA methylation and that detection of these events may be used to improve screening programs. Experimental Design: Seventy-six patients were identified who underwent anal cytology screening and subsequent biopsy at our institution between 1999 and 2004. The specimens from these patients included 184 anal biopsies [normal, n = 57; low-grade squamous intraepithelial lesion (LSIL), n = 74; high-grade squamous intraepithelial lesion (HSIL), n = 41; and invasive SCC, n = 12] and 37 residual liquid-based anal cytology specimens (normal, n = 11; LSIL, n = 12; HSIL, n = 14). The methylation status of the following genes was determined for each biopsy and cytology sample using real-time methylation-specific PCR: HIC1, RASSF1, RARB, CDKN2A, p14, TP73, APC, MLH1, MGMT, DAPK1, and IGSF4. Results: Methylation-specific PCR analysis of biopsy samples revealed that DNA methylation was more common in SCC and HSIL than LSIL and normal mucosa. Specifically, methylation of IGSF4 and DAPK1 was prevalent in SCC (75% and 75% of cases, respectively) and HSIL (59% and 71%, respectively) but was absent in LSIL and normal biopsy samples. Methylation profiles of cytologic samples were similar to those found in the biopsy samples. Conclusions: Aberrant DNA methylation is a frequent event in anal HSIL and SCC. Methylation of IGSF4 and DAPK1 is specific for HSIL and SCC, and may serve as a useful molecular biomarker.

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