BRCA2 Loss-of-Function and High Sensitivity to Cisplatin-Based Chemotherapy in a Patient With a Pleomorphic Soft Tissue Sarcoma: Effect of Genomic Medicine

Camille Tlemsani; Eric Pasmant; Pascaline Boudou-Rouquette; Audrey Bellesoeur; Julien Even; Frédérique Larousserie; Cécile Reyes; David Gentien; Jérôme Alexandre; Michel Vidaud; Philippe Anract; Karen Leroy; François Goldwasser

doi:10.1016/j.amjms.2018.04.015

BRCA2 Loss-of-Function and High Sensitivity to Cisplatin-Based Chemotherapy in a Patient With a Pleomorphic Soft Tissue Sarcoma: Effect of Genomic Medicine

Am J Med Sci. 2018 Oct;356(4):404-407. doi: 10.1016/j.amjms.2018.04.015. Epub 2018 May 1.

Affiliations

¹ Molecular Genetic and Biology Department, Netsarc National Network, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Paris, France; EA7331 Department, Université Paris Descartes, Paris, France; Medical Oncology Department, Netsarc National Network, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Paris,France. Electronic address: [email protected].
² Molecular Genetic and Biology Department, Netsarc National Network, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Paris, France; EA7331 Department, Université Paris Descartes, Paris, France.
³ Medical Oncology Department, Netsarc National Network, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Paris,France.
⁴ Orthopedic Surgery Department, Netsarc National Network, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Paris, France.
⁵ Pathology Department, Sarcoma Center, Netsarc National Network, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Paris, France.
⁶ Translational Research Department, Institut Curie, PSL Research University, Genomics Platform, Paris, France.
⁷ Molecular Genetic and Biology Department, Netsarc National Network, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Paris, France.

PMID: 30041945
DOI: 10.1016/j.amjms.2018.04.015

Abstract

We report the case of a patient with a BRCA2 germline mutation who developed a localized pleomorphic soft tissue sarcoma of the leg with poor prognostic features. BRCA2 germline mutations were not previously reported to be associated with pleomorphic sarcoma. BRCA2 loss-of-heterozygosity was found in the tumor, resulting in a complete BRCA2 loss-of-function. BRCA2 deficiency is associated with sensitivity to cisplatin-based chemotherapy in breast and ovarian cancer patients. We used a cisplatin-based chemotherapy. A rapid major partial response was obtained, which allowed a curative and conservative surgical resection of the sarcoma followed by adjuvant irradiation. This case illustrates that sarcoma patients may present unexpected but targetable genetic abnormalities and that BRCA2 loss-of-function may be targetable in sarcoma as it is associated with enhanced sensitivity to cisplatin. Our observation emphasizes the input of genomic medicine in clinical practice, its importance for treatment decisions, and the overlap between constitutional and somatic genetics.

Keywords: BRCA2; Cancer predisposition; Cisplatin; Genomic medicine; Pleomorphic sarcoma.

Publication types

Case Reports
Review

MeSH terms

Antineoplastic Agents / pharmacology*
BRCA2 Protein / genetics*
BRCA2 Protein / metabolism
Breast Neoplasms / genetics
Cisplatin / pharmacology*
Female
Germ-Line Mutation*
Humans
Loss of Function Mutation*
Middle Aged
Ovarian Neoplasms / genetics
Sarcoma / drug therapy*
Sarcoma / genetics

Substances

Antineoplastic Agents
BRCA2 Protein
BRCA2 protein, human
Cisplatin