Expression of DNA repair genes in ovarian cancer samples: Biological and clinical considerations

Ganzinelli, Monica; Mariani, Pietro; Cattaneo, Dario; Fossati, R.; Fruscio, Robert; Corso, Silvia; Ricci, Francesca; Broggini, Massimo; Damia, Giovanna

doi:10.1016/j.ejca.2010.11.029

Cited by 34 publications

(29 citation statements)

References 47 publications

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“…The gene expression of hTERT and shelterin ( TRF1 , TRF2 , POT1 , TPP1 , RAP1 and TIN2) was quantified by real‐time RT‐PCR as described previously . TNKS (tankyrase 1) and ERCC1 expression was quantified with known primers . The normalized copy number (NCN) for each gene was expressed as the ratio between transcript copy‐numbers of the target and control ( B2M ) genes multiplied by 100.…”

Section: Methodsmentioning

confidence: 99%

ERCC1 and telomere status in breast tumours treated with neoadjuvant chemotherapy and their association with patient prognosis

Gay‐Bellile

Romero

Cayre

et al. 2016

The Journal of Pathology CR

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Dysfunctional telomeres and DNA damage repair (DDR) play important roles in cancer progression. Studies have reported correlations between these factors and tumour aggressiveness and clinical outcome in breast cancer. We studied the characteristics of telomeres and expression of ERCC1, a protein involved in a number of DNA repair pathways and in telomere homeostasis, to assess their prognostic value, alone or in combination, in 90 residual breast tumours after treatment with neoadjuvant chemotherapy (NCT). ERCC1 status was investigated at different molecular levels (protein and gene expression and gene copy‐number variations) by immunohistochemistry, qRT‐PCR and quantitative multiplex fluorescent‐PCR (QMF‐PCR). A comprehensive analysis of telomere characteristics was performed using qPCR for telomere length and qRT‐PCR for telomerase (hTERT), tankyrase 1 (TNKS) and shelterin complex (TRF1, TRF2, POT1, TPP1, RAP1 and TIN2) gene expression. Short telomeres, high hTERT and TNKS expression and low ERCC1 protein expression were independently associated with worse survival outcome. Interestingly, ERCC1 gains and losses correlated with worse disease‐free (p = 0.026) and overall (p = 0.043) survival as compared to survival of patients with normal gene copy‐numbers. Unsupervised hierarchical clustering of all ERCC1 and telomere parameters identified four subgroups with distinct prognosis. In particular, a cluster combining low ERCC1, ERCC1 gene alterations, dysfunctional telomeres and high hTERT and a cluster with high TNKS and shelterin expression correlated with poor disease‐free (HR= 5.41, p= 0.0044) and overall survival (HR= 6.01, p= 0.0023) irrespective of tumour stage and grade. This comprehensive study demonstrates that telomere dysfunction and DDR can contribute synergistically to tumour progression and chemoresistance. These parameters are predictors of clinical outcome in breast cancer patients treated with NCT and could be useful clinically as prognostic biomarkers to tailor adjuvant chemotherapy post‐NCT.

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Section: Methodsmentioning

confidence: 99%

ERCC1 and telomere status in breast tumours treated with neoadjuvant chemotherapy and their association with patient prognosis

Gay‐Bellile

Romero

Cayre

et al. 2016

The Journal of Pathology CR

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“…Loss of FANCA function is associated with hereditary breast and ovarian cancer [9,10]. FANCA variants are a significant risk factor for breast cancer among the population without BRCA1/2 loss [9].…”

Section: Discussionmentioning

confidence: 99%

Aggressive prostate cancer with somatic loss of the homologous recombination repair gene FANCA: a case report

et al. 2020

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Background: Precision medicine based on genomic analysis of germline or tumor tissue is attracting attention. However, there is no consensus on how to apply the results of genomic analysis to treatment. Case presentation: A 59-year-old man diagnosed with metastatic prostate cancer was diagnosed with castrationresistant prostate cancer. Although he was sequentially treated with enzalutamide and abiraterone, bone metastasis progression was identified by skeletal scintigraphy. Therefore, we sequentially performed docetaxel therapy followed by cabazitaxel. After the third cycle of cabazitaxel, his prostate-specific antigen level was stable at < 10 ng/mL, and no radiological progression was detected. The patient's formalin-fixed paraffin-embedded tumor biopsy specimen underwent multiple-gene testing by next-generation sequencing, which identified a FANCA homodeletion. No significant germline mutation was observed. Conclusions: We describe a case of aggressive, castration-resistant prostate cancer with FANCA homodeletion. Genomic analysis of prostate cancer tissue can be useful to determine optimal treatment of such cancers.

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“…Its role as a predictive biomarker of response to platinum-based treatment in the clinic is conflicting. Indeed, while a positive correlation between XPG protein expression and response to chemotherapy was reported26 when the XPG mRNA levels were considered, the correlation was not found27.…”

Section: Discussionmentioning

confidence: 99%

The 5′UTR variant of ERCC5 fails to influence outcomes in ovarian and lung cancer patients undergoing treatment with platinum-based drugs

Rulli

Guffanti

Caiola

et al. 2016

Sci Rep

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The common polymorphic variant in the 5′ untranslated region of the excision repair cross-complementation group 5 (ERCC5) gene was described to generate an upstream open reading frame that regulates both the basal ERCC5 expression and its ability to be synthesized following DNA damage. This variant was reported to affect response to platinum therapy in a cohort of patients with pediatric ependymoma. The role of this variant was investigated in two cohorts of cancer patients, specifically in non-small-cell lung cancer (NSCLC) patients (N = 137) and in epithelial ovarian carcinoma (EOC) patients (N = 240), treated in first-line with platinum-based compounds. Differently from what reported for pediatric ependymoma, the analysis of the polymorphism in NSCLC patients cohort was not able to detect any difference among patients harboring different genotypes both in progression free survival (HR = 0.93; 95%CI 0.64–1.33; p-value = 0.678) and overall survival (HR = 0.90; 95%CI 0.62–1.33; p-value = 0.625). These data were corroborated in a EOC patients cohort, where similar progression free survival (HR = 0.91; 95% CI 0.67–1.24; p-value = 0.561) and overall survival (HR = 0.98; 95% CI 0.71–1.35; p-value = 0.912) were found for the different genotypes. These data, obtained in appropriately sized populations, indicate that the effect of this ERCC5 polymorphism is likely to be relevant only in specific tumors.

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Expression of DNA repair genes in ovarian cancer samples: Biological and clinical considerations

Cited by 34 publications

References 47 publications

ERCC1 and telomere status in breast tumours treated with neoadjuvant chemotherapy and their association with patient prognosis

ERCC1 and telomere status in breast tumours treated with neoadjuvant chemotherapy and their association with patient prognosis

Aggressive prostate cancer with somatic loss of the homologous recombination repair gene FANCA: a case report

The 5′UTR variant of ERCC5 fails to influence outcomes in ovarian and lung cancer patients undergoing treatment with platinum-based drugs

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