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Poly(ADP-ribose) polymerase-1 mRNA expression in human breast cancer: a meta-analysis

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Abstract

Although poly(ADP-ribose) polymerase-1 (PARP1) inhibition is a recent promising therapy in breast cancer, PARP1 expression in this disease is not known. Using DNA microarray and array-based comparative genomic hybridization (arrayCGH), we examined PARP1 mRNA expression and copy number alterations in 326 invasive breast cancer samples and normal breast (NB) samples. A meta-analysis was performed on a large public retrospective gene expression data set (n = 2,485) to analyze correlation between PARP1 mRNA expression and molecular subtypes and clinico-pathological parameters. PARP1 was overexpressed in 58% of cancers, and its expression was heterogeneous between tumors. ArrayCGH data revealed an association between mRNA overexpression and gain/amplification at the PARP1 locus (P < 1.0E-8). Meta-analysis showed that PARP1 expression was higher in basal breast cancers (P < 1.0E-72), but overexpression was also found in other subtypes. PARP1 expression correlated with high grade, medullary histological type, tumor size, and worse metastasis-free survival (MFS; HR = 1.12 [1.04–1.22], P = 0.004) and overall survival (OS; HR = 1.16 [1.04–1.29], P = 0.006). In multivariate analysis, PARP1 expression had an independent prognostic value for MFS, which was restricted to patients untreated with any adjuvant chemotherapy. These data demonstrate overexpression of PARP1 in a large number of breast cancers and support the development of PARP inhibitors in basal subtype, but also potentially in other breast cancer subtypes.

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Abbreviations

PARP1:

Poly(ADP-ribose) polymerase-1

SSBs:

Single-strand breaks

DSBs:

Double-strand breaks

TN:

Triple-negative

NB:

Normal breast

SSP:

Single sample predictor

DWD:

Distance weighted discrimination

aCGH:

Array-comparative genomic hybridization

MFS:

Metastasis-free survival

IHC:

Immunohistochemical

ER:

Estrogen receptor

PR:

Progesterone receptor

References

  1. Ame JC, Spenlehauer C, de Murcia G (2004) The PARP superfamily. Bioessays 26:882–893

    Article  PubMed  CAS  Google Scholar 

  2. Farmer H, McCabe N, Lord CJ, Tutt ANJ, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C et al (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434:917–921

    Article  PubMed  CAS  Google Scholar 

  3. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434:913–917

    Article  PubMed  CAS  Google Scholar 

  4. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O’Connor MJ et al (2009) Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 361:123–134

    Article  PubMed  CAS  Google Scholar 

  5. O’Shaughnessy J, Osborne C, Pippen J, Yoffe M, Patt D, Monaghan G, Rocha C, Ossovskaya V, Sherman B, Bradley C (2009) Efficacy of BSI-201, a poly(ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): results of a randomized phase II trial. J Clin Oncol (Meeting Abstracts) 27:3

    Google Scholar 

  6. Csete B, Lengyel Z, Kadar Z, Battyani Z (2009) Poly(adenosine diphosphate-ribose) polymerase-1 expression in cutaneous malignant melanomas as a new molecular marker of aggressive tumor. Pathol Oncol Res 15:47–53

    Article  PubMed  CAS  Google Scholar 

  7. Staibano S, Pepe S, Lo Muzio L, Somma P, Mascolo M, Argenziano G, Scalvenzi M, Salvatore G, Fabbrocini G, Molea G et al (2005) Poly(adenosine diphosphate-ribose) polymerase 1 expression in malignant melanomas from photoexposed areas of the head and neck region. Hum Pathol 36:724–731

    Article  PubMed  CAS  Google Scholar 

  8. Brustmann H (2007) Poly(adenosine diphosphate-ribose) polymerase expression in serous ovarian carcinoma: correlation with p53, MIB-1, and outcome. Int J Gynecol Pathol 26:147–153

    Article  PubMed  Google Scholar 

  9. Nosho K, Yamamoto H, Mikami M, Taniguchi H, Takahashi T, Adachi Y, Imamura A, Imai K, Shinomura Y (2006) Overexpression of poly(ADP-ribose) polymerase-1 (PARP-1) in the early stage of colorectal carcinogenesis. Eur J Cancer 42:2374–2381

    Article  PubMed  CAS  Google Scholar 

  10. Adelaide J, Finetti P, Bekhouche I, Repellini L, Geneix J, Sircoulomb F, Charafe-Jauffret E, Cervera N, Desplans J, Parzy D et al (2007) Integrated profiling of basal and luminal breast cancers. Cancer Res 67:11565–11575

    Article  PubMed  CAS  Google Scholar 

  11. Bertucci F, Finetti P, Cervera N, Charafe-Jauffret E, Mamessier E, Adelaide J, Debono S, Houvenaeghel G, Maraninchi D, Viens P et al (2006) Gene expression profiling shows medullary breast cancer is a subgroup of basal breast cancers. Cancer Res 66:4636–4644

    Article  PubMed  CAS  Google Scholar 

  12. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4:249–264

    Article  PubMed  Google Scholar 

  13. Hu Z, Fan C, Oh D, Marron JS, He X, Qaqish B, Livasy C, Carey L, Reynolds E, Dressler L et al (2006) The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 7:96

    Article  PubMed  Google Scholar 

  14. Benito M, Parker J, Du Q, Wu J, Xiang D, Perou CM, Marron JS (2004) Adjustment of systematic microarray data biases. Bioinformatics 20:105–114

    Article  PubMed  CAS  Google Scholar 

  15. McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM (2006) REporting recommendations for tumor MARKer prognostic studies (REMARK). Breast Cancer Res Treat 100:229–235

    Article  PubMed  Google Scholar 

  16. Barry WT, Kernagis DN, Dressman HK, Griffis RJ, Hunter JD, Olson JA, Marks JR, Ginsburg GS, Marcom PK, Nevins JR et al (2010) Intratumor heterogeneity and precision of microarray-based predictors of breast cancer biology and clinical outcome. J Clin Oncol 28:2198–2206

    Article  PubMed  Google Scholar 

  17. Bieche I, Champeme MH, Lidereau R (1995) Loss and gain of distinct regions of chromosome 1q in primary breast cancer. Clin Cancer Res 1:123–127

    PubMed  CAS  Google Scholar 

  18. Knuutila S, Autio K, Aalto Y (2000) Online access to CGH data of DNA sequence copy number changes. Am J Pathol 157:689

    Article  PubMed  CAS  Google Scholar 

  19. Larramendy ML, Lushnikova T, Bjorkqvist AM, Wistuba II, Virmani AK, Shivapurkar N, Gazdar AF, Knuutila S (2000) Comparative genomic hybridization reveals complex genetic changes in primary breast cancer tumors and their cell lines. Cancer Genet Cytogenet 119:132–138

    Article  PubMed  CAS  Google Scholar 

  20. Cleator S, Heller W, Coombes RC (2007) Triple-negative breast cancer: therapeutic options. Lancet Oncol 8:235–244

    Article  PubMed  Google Scholar 

  21. Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, Mierzwa T, Szwiec M, Wisniowski R, Siolek M et al (2010) Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol 28:375–379

    Article  PubMed  CAS  Google Scholar 

  22. Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, Juul N, Leong C-O, Calogrias D, Buraimoh A et al (2010) Efficacy of neoadjuvant cisplatin in triple-negative breast cancer. J Clin Oncol 28:1145–1153

    Google Scholar 

  23. von Minckwitz G, Müller B, Loibl S, Blohmer JU, duBois A, Huober J, Kandolf R, Budczies J, Denkert C (2010) PARP is expressed in all subtypes of early breast cancer and is a predictive factor for response to neoadjuvant chemotherapy. Eur J Cancer Suppl 8(3):188

    Article  Google Scholar 

  24. Loibl S, Mueller B, Von Minckwitz G, Blohmer JU, Bois Ad, Huober JB, Fend F, Budczies J, Denkert C (2010) PARP expression in early breast cancer and its predictive value for response to neoadjuvant chemotherapy. J Clin Oncol (Meeting Abstracts) 28:10511

  25. Mendes-Pereira AM, Martin SA, Brough R, McCarthy A, Taylor JR, Kim J-S, Waldman T, Lord CJ, Ashworth A (2009) Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors. EMBO Mol Med 1:315–322

    Article  PubMed  CAS  Google Scholar 

  26. Hegan DC, Lu Y, Stachelek GC, Crosby ME, Bindra RS, Glazer PM (2010) Inhibition of poly(ADP-ribose) polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130. Proc Natl Acad Sci 107:2201–2206

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study is supported by Institut Paoli-Calmettes, Inserm, Institut National du Cancer (Tr 2008), Association pour le Recherche contre le Cancer, Ligue Nationale contre le Cancer (label DB), Ligue contre le Cancer (comité Corse du Sud), and Fondation pour la Recherche Médicale (RS 2009).

Conflict of interest

None.

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Authors and Affiliations

  1. Département d’Oncologie Médicale and U891 INSERM, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, 232 Bd. Ste-Marguerite, 13009, Marseille, France

    Anthony Gonçalves, Renaud Sabatier, Marine Gilabert, Patrice Viens & François Bertucci

  2. Département de Pharmacologie Moléculaire and U891 INSERM, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France

    Anthony Gonçalves, Marine Gilabert & Jean-Paul Borg

  3. Département d’Oncologie Moléculaire and U891 INSERM, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France

    Pascal Finetti, Renaud Sabatier, José Adelaide, Max Chaffanet, Daniel Birnbaum & François Bertucci

  4. Université de la Méditerranée, Marseille, France

    Anthony Gonçalves, Jean-Paul Borg, Patrice Viens & François Bertucci

Authors
  1. Anthony Gonçalves
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  2. Pascal Finetti
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  3. Renaud Sabatier
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  4. Marine Gilabert
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  5. José Adelaide
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  7. Max Chaffanet
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  8. Patrice Viens
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  9. Daniel Birnbaum
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  10. François Bertucci
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Correspondence to Anthony Gonçalves.

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Gonçalves, A., Finetti, P., Sabatier, R. et al. Poly(ADP-ribose) polymerase-1 mRNA expression in human breast cancer: a meta-analysis. Breast Cancer Res Treat 127, 273–281 (2011). https://doi.org/10.1007/s10549-010-1199-y

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  • DOI: https://doi.org/10.1007/s10549-010-1199-y

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