Clinical actionability of BRCA2 alterations in uterine leiomyosarcoma: a molecular tumor board case report and a cBioPortal comprehensive analysis Journal Article
| Authors: | Bielo, L. B.; Repetto, M.; Crimini, E.; Belli, C.; Setola, E.; Parma, G.; Fusco, N.; Barberis, M.; Rocco, E. G.; Marra, A.; Colombo, N.; Curigliano, G. |
| Article Title: | Clinical actionability of BRCA2 alterations in uterine leiomyosarcoma: a molecular tumor board case report and a cBioPortal comprehensive analysis |
| Abstract: | Background: Uterine leiomyosarcoma (uLMS) represents one of the most common sarcoma histotypes, demonstrating an overall dismal prognosis. Previous studies reported uLMS to carry recurrent somatic BRCA2 homozygous deletions, related to significant clinical benefits from the use of PARP inhibitors. Methods: To investigate the prevalence in uLMS of genomic alterations (alt) in BRCA2 and other homologous recombination (HR) and DNA damage response (DDR) genes, cBioPortal was accessed and data were retrieved from studies including pan-sarcoma histologies. HR-/DDR-genes included BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, NBN, PALB2, RAD51C, RAD51D, RAD50, and ATR. Only oncogenic/likely oncogenic alterations were included according to OncoKB. Clinical Report and Results: We reported a clinical case of a patient affected by a highly pretreated uLMS discussed at the European Institute of Oncology Molecular Tumor Board. A targeted next-generation sequencing panel demonstrated a somatic BRCA2 homozygous deletion (homDel). Upon access to Niraparib, a remarkable response of 15 months was observed before experiencing disease progression. In the genomic query, among 2393 cases, uLMS (n = 193) displayed 9 of all 31 BRCA2alt observed, representing the only sarcoma histotype showing an enrichment in BRCA2alt (4.66%; q < 0.001). All of 9 BRCA2alt were represented by homDel, which related to a high fraction of genome altered. Conclusion: uLMS displays a significant frequency of somatic BRCA2alt homDel. Considering their dismal prognosis, further investigation is warranted to test the use of PARPi in uLMS, and particularly in the setting of BRCA1/2 alterations. © The Author(s) 2024. Published by Oxford University Press. |
| Keywords: | adult; clinical article; human tissue; middle aged; genetics; mutation; case report; doxorubicin; gemcitabine; adjuvant therapy; follow up; hysterectomy; rad50 protein; homologous recombination; dacarbazine; multiple cycle treatment; pathology; brca1 protein; brca2 protein; docetaxel; sarcoma; tumor suppressor gene; pazopanib; dna damage response; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor; checkpoint kinase 2; trabectedin; leiomyosarcoma; drug therapy; checkpoint kinase 1; malignant peripheral nerve sheath tumor; good clinical practice; uterine neoplasms; disease exacerbation; uterine leiomyosarcoma; uterus tumor; fanconi anemia group l protein; fanconi anemia group d2 protein; fanconi anemia group c protein; brca1 associated ring domain protein 1; fanconi anemia group a protein; genomic alteration; multiplex ligation dependent probe amplification; fanconi anemia group e protein; fanconi anemia group f protein; fanconi anemia group g protein; high throughput sequencing; next-generation sequencing; brca2 protein, human; niraparib; humans; human; female; article; poly(adp-ribose) polymerase inhibitors; partner and localizer of brca2; brca2 homozygous deletion; bilateral hysteroannessiectomy |
| Journal Title: | The Oncologist |
| Volume: | 29 |
| Issue: | 7 |
| ISSN: | 1083-7159 |
| Publisher: | Oxford University Press |
| Date Published: | 2024-07-01 |
| Start Page: | 560 |
| End Page: | 565 |
| Language: | English |
| DOI: | 10.1093/oncolo/oyae082 |
| PUBMED: | 38716772 |
| PROVIDER: | scopus |
| PMCID: | PMC11224980 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
