Circulating cell-free DNA: A promising marker of regional lymphonode metastasis in breast cancer patients

M. Agostini, M. V. Enzo, C. Bedin, V. Belardinelli, E. Goldin, P. Del Bianco, E. Maschietto, E. D'Angelo, Leo Izzi, A. Saccani, G. Zavagno, D. Nitti

Research output: Contribution to journalArticle

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Abstract

Purpose: We undertook the current study with untreated breast cancer to (1) role the variations in the plasma levels of cfDNA and the size distribution in early stage, (2) determine the frequency in plasma of methylation of three candidate genes, RASSF1A, MAL, and SFRP1, and (3) to determine whether detection of cfDNA variations and methylation changes in plasma might have specific clinical utility. Methods and materials: Thirty-nine patients woman patients (median age 64 years; range, 36-90 years) who underwent surgery for primary BR and 49 healthy females' subjects (control group without any breast lesion) were evaluated. The cfDNA levels were analyzed using quantitative real-time polymerase chain reaction of β-globin. Based on the ALU repeats, the cfDNA was considered as either total (fragments of 115 bp, ALU115) or tumoral (fragments of 247 bp, ALU247). The association between the levels of the ALU247, ALU115 repeat, and ALU 247/115and the pathologic tumor characteristics was analyzed. Used methylight qPCR method, cfDNA from plasma samples of healthy donors and patients with breast cancer were evaluated for the diagnotic value of the methylation status of three genes (RASSF1A, MAL, SFRP1) frequently methylated in breast cancer. Results: The baseline levels of cfDNA were significantly higher in the patients with cancer, and the level of ALU247 was the most accurate circulating cfDNA marker in discriminating the cancer from non-cancer subjects. A high statistical significance was found by considering the T stage and patients with regional LN metastasis positive cancers showed significantly higher cfDNA level of ALU247. Moreover, patients with methylation of at least one of the gene under investigate showed a higher quantity of cfDNA ALU115 (p<0.0001) and ALU247 level (p<0.0001). Conclusions: We observed that necrosis could be a potential source of circulating tumour-specific cfDNA ALU247; and that cfDNA ALU247 and methylated cfDNA (RASSF1A, MAL and SFRP1) are both a phenotypic feature of tumour biology.

Original languageEnglish
Pages (from-to)89-98
Number of pages10
JournalCancer Biomarkers
Volume11
Issue number2-3
DOIs
Publication statusPublished - 2012

Fingerprint

Breast Neoplasms
Neoplasm Metastasis
Methylation
DNA
Neoplasms
Genes
Globins
Real-Time Polymerase Chain Reaction
Healthy Volunteers
Breast
Necrosis
Tissue Donors
Control Groups

Keywords

  • Breast cancer
  • cfDNA
  • regional LN metastasis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Genetics

Cite this

Circulating cell-free DNA : A promising marker of regional lymphonode metastasis in breast cancer patients. / Agostini, M.; Enzo, M. V.; Bedin, C.; Belardinelli, V.; Goldin, E.; Del Bianco, P.; Maschietto, E.; D'Angelo, E.; Izzi, Leo; Saccani, A.; Zavagno, G.; Nitti, D.

In: Cancer Biomarkers, Vol. 11, No. 2-3, 2012, p. 89-98.

Research output: Contribution to journalArticle

Agostini, M, Enzo, MV, Bedin, C, Belardinelli, V, Goldin, E, Del Bianco, P, Maschietto, E, D'Angelo, E, Izzi, L, Saccani, A, Zavagno, G & Nitti, D 2012, 'Circulating cell-free DNA: A promising marker of regional lymphonode metastasis in breast cancer patients', Cancer Biomarkers, vol. 11, no. 2-3, pp. 89-98. https://doi.org/10.3233/CBM-2012-0263
Agostini, M. ; Enzo, M. V. ; Bedin, C. ; Belardinelli, V. ; Goldin, E. ; Del Bianco, P. ; Maschietto, E. ; D'Angelo, E. ; Izzi, Leo ; Saccani, A. ; Zavagno, G. ; Nitti, D. / Circulating cell-free DNA : A promising marker of regional lymphonode metastasis in breast cancer patients. In: Cancer Biomarkers. 2012 ; Vol. 11, No. 2-3. pp. 89-98.
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T2 - A promising marker of regional lymphonode metastasis in breast cancer patients

AU - Agostini, M.

AU - Enzo, M. V.

AU - Bedin, C.

AU - Belardinelli, V.

AU - Goldin, E.

AU - Del Bianco, P.

AU - Maschietto, E.

AU - D'Angelo, E.

AU - Izzi, Leo

AU - Saccani, A.

AU - Zavagno, G.

AU - Nitti, D.

PY - 2012

Y1 - 2012

N2 - Purpose: We undertook the current study with untreated breast cancer to (1) role the variations in the plasma levels of cfDNA and the size distribution in early stage, (2) determine the frequency in plasma of methylation of three candidate genes, RASSF1A, MAL, and SFRP1, and (3) to determine whether detection of cfDNA variations and methylation changes in plasma might have specific clinical utility. Methods and materials: Thirty-nine patients woman patients (median age 64 years; range, 36-90 years) who underwent surgery for primary BR and 49 healthy females' subjects (control group without any breast lesion) were evaluated. The cfDNA levels were analyzed using quantitative real-time polymerase chain reaction of β-globin. Based on the ALU repeats, the cfDNA was considered as either total (fragments of 115 bp, ALU115) or tumoral (fragments of 247 bp, ALU247). The association between the levels of the ALU247, ALU115 repeat, and ALU 247/115and the pathologic tumor characteristics was analyzed. Used methylight qPCR method, cfDNA from plasma samples of healthy donors and patients with breast cancer were evaluated for the diagnotic value of the methylation status of three genes (RASSF1A, MAL, SFRP1) frequently methylated in breast cancer. Results: The baseline levels of cfDNA were significantly higher in the patients with cancer, and the level of ALU247 was the most accurate circulating cfDNA marker in discriminating the cancer from non-cancer subjects. A high statistical significance was found by considering the T stage and patients with regional LN metastasis positive cancers showed significantly higher cfDNA level of ALU247. Moreover, patients with methylation of at least one of the gene under investigate showed a higher quantity of cfDNA ALU115 (p<0.0001) and ALU247 level (p<0.0001). Conclusions: We observed that necrosis could be a potential source of circulating tumour-specific cfDNA ALU247; and that cfDNA ALU247 and methylated cfDNA (RASSF1A, MAL and SFRP1) are both a phenotypic feature of tumour biology.

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KW - Breast cancer

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KW - regional LN metastasis

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