DNA Repair Deficiency in Breast Cancer: Opportunities for Immunotherapy

Gilmore, Elaine S.; McCabe, Nuala; Kennedy, Richard D.; Parkes, Eileen E.

doi:10.1155/2019/4325105

Cited by 22 publications

(15 citation statements)

References 166 publications

(148 reference statements)

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“…Assessing the presence of pathogenic somatic variants in CHEK2 and PALB2 genes is not common practice. In breast cancer patients, somatic changes may be present in other genes involved in DNA repair: (1) homologous recombination ( ATM , ATR , CHEK1 , CHEK2 , BARD1 , RAD51 , NBS1 , PALB2 , FANCD2 ), (2) non-homologous end joining ( DNA-PK , KU70/80 ), (3) mismatch repair ( MLH1 , MSH1 , MSH6 , PMS2 ), (4) base excision repair ( APE1 , XRCC1 , ERCC2 ) [ 40 ]. It is worth highlighting that there are different commercial panel tests to examine a wide range of genes related to breast cancer employing the NGS technique.…”

Section: Discussionmentioning

confidence: 99%

BRCA1/2 Mutation Detection in the Tumor Tissue from Selected Polish Patients with Breast Cancer Using Next Generation Sequencing

Szczerba

Kamińska²,

Mierzwa³

et al. 2021

Genes

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(1) Background: Although, in the mutated BRCA detected in the Polish population of patients with breast cancer, there is a large percentage of recurrent pathogenic variants, an increasing need for the assessment of rare BRCA1/2 variants using NGS can be observed. (2) Methods: We studied 75 selected patients with breast cancer (negative for the presence of 5 mutations tested in the Polish population in the prophylactic National Cancer Control Program). DNA extracted from the cancer tissue of these patients was used to prepare a library and to sequence all coding regions of the BRCA1/2 genes. (3) Results: We detected nine pathogenic variants in 8 out of 75 selected patients (10.7%). We identified one somatic and eight germline variants. We also used different bioinformatic NGS software programs to analyze NGS FASTQ files and established that tertiary analysis performed with different tools was more likely to give the same outcome if we analyzed files received from secondary analysis using the same method. (4) Conclusions: Our study emphasizes (i) the importance of an NGS validation process with a bioinformatic procedure included; (ii) the importance of screening both somatic and germline pathogenic variants; (iii) the urgent need to identify additional susceptible genes in order to explain the high percentage of non-BRCA-related hereditary cases of breast cancer.

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Section: Discussionmentioning

confidence: 99%

BRCA1/2 Mutation Detection in the Tumor Tissue from Selected Polish Patients with Breast Cancer Using Next Generation Sequencing

Szczerba

Kamińska²,

Mierzwa³

et al. 2021

Genes

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“…PARPi have shown effectiveness in tumors with deficiencies in our DEGs such as RAD51, FANCD2, FANCA, CHK1 and XRCC2 [ 118 – 120 ]. For BRCA1/2 mutant breast cancers, PARPi olaparib and talazoparib are now FDA-approved monotherapies [ 119 , 121 , 122 ]. Other studies also showed that their effectiveness extend to tumors without BRCA-mutations [ 117 , 123 ].…”

Section: Discussionmentioning

confidence: 99%

“…For example, PARP inhibitors (PARPi) serve as an example of the targeted therapy [117]. PARPi have shown effectiveness in tumors with deficiencies in our DEGs such as RAD51, FANCD2, FANCA, CHK1 and XRCC2 [118][119][120]. For BRCA1/2 mutant breast cancers, PARPi olaparib and talazoparib are now FDA-approved monotherapies [119,121,122].…”

Section: Implications Of Overexpression Of Dna Repair Genes On Precismentioning

confidence: 99%

The overexpression of DNA repair genes in invasive ductal and lobular breast carcinomas: Insights on individual variations and precision medicine

et al. 2021

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In the era of precision medicine, analyzing the transcriptomic profile of patients is essential to tailor the appropriate therapy. In this study, we explored transcriptional differences between two invasive breast cancer subtypes; infiltrating ductal carcinoma (IDC) and lobular carcinoma (LC) using RNA-Seq data deposited in the TCGA-BRCA project. We revealed 3854 differentially expressed genes between normal ductal tissues and IDC. In addition, IDC to LC comparison resulted in 663 differentially expressed genes. We then focused on DNA repair genes because of their known effects on patients’ response to therapy and resistance. We here report that 36 DNA repair genes are overexpressed in a significant number of both IDC and LC patients’ samples. Despite the upregulation in a significant number of samples, we observed a noticeable variation in the expression levels of the repair genes across patients of the same cancer subtype. The same trend is valid for the expression of miRNAs, where remarkable variations between patients’ samples of the same cancer subtype are also observed. These individual variations could lie behind the differential response of patients to treatment. The future of cancer diagnostics and therapy will inevitably depend on high-throughput genomic and transcriptomic data analysis. However, we propose that performing analysis on individual patients rather than a big set of patients’ samples will be necessary to ensure that the best treatment is determined, and therapy resistance is reduced.

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“…The multiple cancer mutations taking place in humans are continuously corrected by the immune cells. However, if the number or function of the immune cells decreases, there may be an increased risk of cancer development (Dunn, Bruce, Ikeda, Old, & Schreiber, 2002;Gilmore, Mccabe, Kennedy, & Parkes, 2019).…”

Section: Risk Of Bias Highmentioning

confidence: 99%

The effects of long‐term opioid treatment on the immune system in chronic non‐cancer pain patients: A systematic review

Diasso

Birke

Nielsen

et al. 2019

European Journal of Pain

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Background and objective Opioids have been increasingly prescribed for chronic non‐cancer pain (CNCP). An association between long‐term opioid treatment (L‐TOT) of CNCP patients and suppression of both the innate and the adaptive immune system has been proposed. This systematic review aims at investigating the effects of L‐TOT on the immune system in CNCP patients. Databases and data treatment A systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and the CINAHL for relevant articles was performed. Studies examining measures of both the innate and the adaptive immune system in adult CNCP patients in L‐TOT (≥4 weeks of intake) were included. Outcomes and the level of evidence were analysed. Results A total of 382 studies were identified; however, 376 were excluded (352 inappropriate methodology, 21 duplicates, three full‐text could not be obtained) and one randomized controlled trial (RCT) and five cross‐sectional studies were included and analysed. L‐TOT compared with no treatment was associated with a lower percentage of natural killer (NK) cells, a lower absolute number of CD56bright NK cells, a higher absolute number of IL‐2‐activated NK cells and a higher concentration of IL‐1β as a response to toll‐like receptor (TLR) agonists stimulation (Pam3CSK4, LPS, Imiquimod). No other significant differences were reported. Generalizability of the results was limited due to inconsistency of outcomes and an overall low quality of the studies. Conclusions L‐TOT may alter the immune system in CNCP patients, but the level of evidence is still weak. More studies are needed to clarify the impact of L‐TOT on immune system function. Significance This systematic review found indication that long‐term opioid treatment alters the immune system in chronic non‐cancer pain patients. These alterations involved the NK cells and IL‐1β production. However, the level of evidence is weak.

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DNA Repair Deficiency in Breast Cancer: Opportunities for Immunotherapy

Cited by 22 publications

References 166 publications

BRCA1/2 Mutation Detection in the Tumor Tissue from Selected Polish Patients with Breast Cancer Using Next Generation Sequencing

BRCA1/2 Mutation Detection in the Tumor Tissue from Selected Polish Patients with Breast Cancer Using Next Generation Sequencing

The overexpression of DNA repair genes in invasive ductal and lobular breast carcinomas: Insights on individual variations and precision medicine

The effects of long‐term opioid treatment on the immune system in chronic non‐cancer pain patients: A systematic review

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