Casolino, R. et al. (2021) Homologous recombination deficiency in pancreatic cancer: a systematic review and prevalence meta-analysis. Journal of Clinical Oncology, 39(23), pp. 2617-2631. (doi: 10.1200/JCO.20.03238) (PMID:34197182) (PMCID:PMC8331063)
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Abstract
Purpose: To analyze the prevalence of homologous recombination deficiency (HRD) in patients with pancreatic ductal adenocarcinoma (PDAC). Materials and Methods: We conducted a systematic review and meta-analysis of the prevalence of HRD in PDAC from PubMed, Scopus, and Cochrane Library databases, and online cancer genomic data sets. The main outcome was pooled prevalence of somatic and germline mutations in the better characterized HRD genes (BRCA1, BRCA2, PALB2, ATM, ATR, CHEK2, RAD51, and the FANC genes). The secondary outcomes were prevalence of germline mutations overall, and in sporadic and familial cases; prevalence of germline BRCA1/2 mutations in Ashkenazi Jewish (AJ); and prevalence of HRD based on other definitions (ie, alterations in other genes, genomic scars, and mutational signatures). Random-effects modeling with the Freeman-Tukey transformation was used for the analyses. PROSPERO registration number: (CRD42020190813). Results: Sixty studies with 21,842 participants were included in the systematic review and 57 in the meta-analysis. Prevalence of germline and somatic mutations was BRCA1: 0.9%, BRCA2: 3.5%, PALB2: 0.2%, ATM: 2.2%, CHEK2: 0.3%, FANC: 0.5%, RAD51: 0.0%, and ATR: 0.1%. Prevalence of germline mutations was BRCA1: 0.9% (2.4% in AJ), BRCA2: 3.8% (8.2% in AJ), PALB2: 0.2%, ATM: 2%, CHEK2: 0.3%, and FANC: 0.4%. No significant differences between sporadic and familial cases were identified. HRD prevalence ranged between 14.5%-16.5% through targeted next-generation sequencing and 24%-44% through whole-genome or whole-exome sequencing allowing complementary genomic analysis, including genomic scars and other signatures (surrogate markers of HRD). Conclusion: Surrogate readouts of HRD identify a greater proportion of patients with HRD than analyses limited to gene-level approaches. There is a clear need to harmonize HRD definitions and to validate the optimal biomarker for treatment selection. Universal HRD screening including integrated somatic and germline analysis should be offered to all patients with PDAC.
| Item Type: | Articles |
|---|---|
| Additional Information: | Funding: Associazione Italiana Ricerca Cancro (AIRC 5x1000 no. 18718). Associazione Italiana Ricerca Cancro (AIRC 5x1000 no. 12182). Fondazione Italiana Malattie Pancreas—Italian Ministry of Health (CUP_J38D19000690001). Fondazione Cariverona: Oncology Biobank Project Antonio Schiavi (prot. 203885/2017). Cancer Research UK C29717/A17263, C29717/A18484, C596/A18076, C596/A20921, C29717/A23526. Wellcome Trust Senior Investigator Award: 103721/Z/ 14/Z. Pancreatic Cancer UK Future Research Leaders Fund FLF2015_04_Glasgow. Scottish Genomes Partnership SEHHD-CSO 1175759/2158447. MRC/EPSRC Glasgow Molecular Pathology Node MR/N005813/1. The Howat Foundation. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Braconi, Professor Chiara and Biankin, Professor Andrew and pea, Dr Antonio and Casolino, Dr Raffaella and Froeling, Dr Fieke and Chang, Professor David |
| Authors: | Casolino, R., Paiella, S., Azzolina, D., Beer, P. A., Corbo, V., Lorenzoni, G., Gregori, D., GOlan, T., Braconi, C., Froeling, F. E.M., Milella, M., Scarpa, A., Pea, A., Malleo, G., Salvia, R., Bassi, C., Chang, D. K., and Biankin, A. V. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Journal of Clinical Oncology |
| Publisher: | American Society of Clinical Oncology |
| ISSN: | 0732-183X |
| ISSN (Online): | 1527-7755 |
| Published Online: | 01 July 2021 |
| Copyright Holders: | Copyright © 2021 American Society of Clinical Oncology |
| First Published: | First published in Journal of Clinical Oncology 39(23): 2617-2631 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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