Persistence of tumor DNA in plasma of breast cancer patients after mastectomy
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Background: We investigated tumor DNA changes before and after mastectomy in the plasma of breast cancer patients with no disseminated disease and eventually investigated these changes’ relationship to specific pathological parameters of the tumors.
Methods: We studied 41 patients. DNA extracted from tumor and normal breast tissues, mononuclear blood cells, and plasma was used for molecular studies. Alterations in the microsatellite markers D17S855, D17S654, D16S421, TH2, D10S197, and D9S161, as well as point mutations in the p53 gene and aberrant methylation of p16INK4a, were used to identify and characterize tumor and plasma DNA. A number of tumor clinicopathological parameters were analyzed in each patient.
Results: We found that 18 (44%) of the 27 patients with alterations in tumor DNA presented the same plasma DNA alteration before mastectomy, and persistence of the same molecular features was detected in plasma DNA 4 to 6 weeks postmastectomy in 8 (19.5%) patients. Patients with vascular invasion, more than three lymph node metastases, and higher histological grade at diagnosis displayed plasma DNA after mastectomy with a significant difference.
Conclusions: Persistence of plasma DNA with features of tumor DNA may be present after mastectomy in breast cancer patients, and its relation to bad-prognosis histological parameters may suggest undetectable micrometastatic disease.
- Wingo PA, Tong T, Golden S. Cancer statistics.CA Cancer J Clin 1995;45:8–30. CrossRef
- Weinberg RA. Tumor suppressor genes.Science 1991;254:1138–46. CrossRef
- Sjögren S, Inganäs M, Norberg T, et al. The p53 gene in breast cancer: prognostic value of complementary DNA sequencing versus immunohistochemistry.J Natl Cancer Inst 1996;88:173–82. CrossRef
- Crook T, Crossland S, Crompton MR, Osin P, Gusterson BA. p53 mutations in BRCA1-associated familial breast cancer.Lancet 1997;350:638–9. CrossRef
- Patel U, Grundfest-Broniatwoski S, Gupta M, Banerjee S. Microsatellite instabilities at five chromosomes in primary breast tumors.Oncogene 1994;9:3695–700.
- Toyama T, Iwase M, Yamashita H, et al. Microsatellite instability in sporadic human breast cancer.Int J Cancer 1996;68:447–51. CrossRef
- Phelan CM, Borg A, Cuny M, et al. Consortium study on 1280 breast carcinomas: allelic loss on chromosome 17 target subregions associated with family history and clinical parameters.Cancer Res 1998;58:1004–12.
- Deng G, Lu Y, Zlotnikov G, Thor AN, Smith HS. Loss of heterozygosity in normal tissue adjacent to breast carcinomas.Science 1996;274:2057–9. CrossRef
- Silva JM, Gonzalez R, Provencio M, et al. Loss of heterozygosity in bRCA1 and BRCA2 markers and high-grade malignancy in breast cancer.Breast Cancer Res Treat 1999;53:9–17. CrossRef
- Herman JG, Merlo A, Mao L, et al. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers.Cancer Res 1995;55:4525–30.
- Mao L, Hruban RH, Boyle JO, Tockman M, Sidransky D. Detection of oncogene mutations in sputum precedes diagnosis of lung cancer.Cancer Res 1994;54:1634–7.
- Sidransky D, Von Eschenbach A, Tsai YC, et al. Identification of p53 gene mutations in bladder cancers and urine samples.Science 1991;252:706–9. CrossRef
- Kondo H, Sugano K, Fukamaya N, et al. Detection of point mutations in the K-ras oncogene at codon 12 in pure pancreatic juice for diagnosis of pancreatic carcinoma.Cancer 1994;73:1589–94. CrossRef
- Sidransky D, Tokino T, Hamilton SR, et al. Identification of ras oncogene mutations in the stool of patients with curable colorectal tumors.Science 1992;256:102–5. CrossRef
- Motomura K, Koyama H, Noguchi S, Inaji H, Azuma C. Detection of c-erbB-2 gene amplification in nipple discharge by means of polymerase chain reaction.Breast Cancer Res Treat 1995;33:89–92. CrossRef
- Chen XQ, Stroun M, Magnenat JL, et al. Microsatellite alterations in plasma DNA of small cell lung cancer patients.Nat Med 1996;2:1033–5. CrossRef
- Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB, Herman JG. Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients.Cancer Res 1999;59:67–70.
- Silva JM, Dominguez G, Garcia JM, et al. Presence of tumor DNA in plasma of breast cancer patients: clinicopathological correlations.Cancer Res 1999;59:3251–6.
- Chen X, Bonnefoi H, Diebol-Berger S, et al. Detecting tumor-related alterations in plasma or serum DNA of patients diagnosed with breast cancer.Clin Cancer Res 1999;5:2297–303.
- Mayall F, Fairweather S, Wilkins R, Chang B, Nicholls R. Microsatellite abnormalities in plasma of patients with breast carcinoma: concordance with the primary tumour.J Clin Pathol 1999;52:363–6. CrossRef
- Shaw JA, Smith BM, Walsh T, et al. Microsatellite alterations in plasma DNA of primary breast cancer patients.Clin Cancer Res 2000;6:1119–24.
- Anker P, Lefort F, Vasioukhin V, et al. K-ras mutations are found in DNA extracted from the plasma of patients with colorectal cancer.Gastroenterology 1997;112:1114–20. CrossRef
- Hibi K, Robinson CR, Booker S, et al. Molecular detection of genetic alterations in serum of colorectal cancer patients.Cancer Res 1998;58:1405–7.
- Castells A, Puig P, Mora J, et al. K-ras mutations in DNA extracted from the plasma of patients with pancreatic carcinoma: diagnostic utility and prognostic significance.J Clin Oncol 1999;17:578–84.
- Leon SA, Shapiro B, Sklaroff DM, Yaros J. Free DNA in the serum of cancer patients and the effect of therapy.Cancer Res 1977;37:646–50.
- Anderson LA, Friedman L, Osborne-Lawrence S, et al. High-density genetic map of the BRCA1 region of chromosome 17q12-q21.Genomics 1993;17:618–23. CrossRef
- Steiner G, Schoenberg MP, Linn JF, Mao L, Sidransky D. Detection of bladder cancer recurrence by microsatellite analysis of urine.Nat Med 1997;3:621–4. CrossRef
- Skirnisdottir S, Eiriksdottir G, Baldursson T, Barkardottir RB, Egilsson V, Ingvarsson S. High frequency of allelic imbalance at chromosome region 16q22–23 in human breast cancer: correlation with high PgR and low S phase.Int J Cancer 1995;64:112–6. CrossRef
- Brenner AJ, Aldaz CM. Chromosome 9p allelic loss and p16/CDKN2 in breast cancer and evidence of p16 inactivation in immortal breast epithelial cells.Cancer Res 1995;55:2892–5.
- Oto M, Miyake S, Yuasa Y. Optimization of nonradioisotopic single strand conformation polymorphism analysis with a conventional minislab gel electrophoresis apparatus.Anal Biochem 1993;213:19–22. CrossRef
- Orita M, Suzuki Y, Sekiya T, Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction.Genomics 1989;5:874–9. CrossRef
- Silva JM, Gonzalez R, Dominguez G, Garcia JM, España P, Bonilla F. TP53 gene mutations in plasma DNA of cancer patients.Genes Chromosomes Cancer 1999;24:160–1. CrossRef
- Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB. Methylation specific PCR: a novel PCR assay for methylation status of CpG islands.Proc Natl Acad Sci U S A 1996;93:9821–6. CrossRef
- Lo YMD, Chan LYS, Lo KW, et al. Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinomas.Cancer Res 1999;59:1188–91.
- Lo YMD, Zhang J, Leung TN, Lau TK, Chang AM, Hjelm NM. Rapid clearance of fetal DNA from maternal plasma.Am J Hum Genet 1999;64:218–24. CrossRef
- Persistence of tumor DNA in plasma of breast cancer patients after mastectomy
Annals of Surgical Oncology
Volume 9, Issue 1 , pp 71-76
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Mammary malignancies
- Circulating DNA
- Poor prognosis
- Genetic markers
- Industry Sectors
- Author Affiliations
- 1. Department of Medical Oncology, Molecular Genetics Unit, Clinica Puerta de Hierro, C/San Martin de Porres, 4, 28035, Madrid, Spain
- 2. the Department of Pathology, Hospital Militar del Aire, Madrid, Spain