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  • Chemoresistant pleomorphic rhabdomyosarcoma: whole exome sequencing reveals underlying cancer predisposition and therapeutic options

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Cancer genetics
Short report
Chemoresistant pleomorphic rhabdomyosarcoma: whole exome sequencing reveals underlying cancer predisposition and therapeutic options
  1. Camille Tlemsani1,2,3,
  2. Karen Leroy1,4,
  3. Anne-Paule Gimenez-Roqueplo5,6,
  4. Audrey Mansuet-Lupo4,7,
  5. Eric Pasmant1,3,
  6. Frederique Larousserie4,7,
  7. Pascaline Boudou-Rouquette2,4,
  8. Michel Vidaud1,3,
  9. Jacques Cadranel8,
  10. Helene Blons9,10,
  11. Francois Goldwasser2,4,
  12. Pierre Laurent-Puig5,9
  1. 1 Service de Génétique et Biologie Moléculaires, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris, France
  2. 2 Service d’Oncologie Médicale, Sarcoma center, Netsarc National Network, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris, France
  3. 3 EA7331, Université Paris Descartes, Faculté de Pharmacie de Paris, Paris, France
  4. 4 Faculté de médecine, Université Paris Descartes, Paris, France
  5. 5 Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France
  6. 6 INSERM UMR-970, Paris Cardiovascular Research Center, Paris, France
  7. 7 Service d’Anatomopathologie, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Assistance Publique Hôpitaux de Paris, Paris, France
  8. 8 Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Service de Pneumologie and Sorbonne Université, Paris, France
  9. 9 INSERM UMR-S1147, Université Sorbonne-Paris-Cité, Paris, France
  10. 10 Service de Biochimie, Pharmacologie et Biologie Moléculaire, Hôpital Européen Georges-Pompidou, Assistance Publique Hôpitaux de Paris, Paris, France
  1. Correspondence to Dr Camille Tlemsani, Service d’Oncologie Médicale, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, AP-HP, Paris 75014, France; camille.tlemsani{at}aphp.fr

Abstract

Background Rhabdomyosarcoma (RMS) is rare cancer affecting children and adults. Pleomorphic RMS histology is almost exclusive to adult patients and often resistant to chemotherapy.

Objective We report the case of a 19-year-old patient who presented with a metastatic chemoresistant pleomorphic RMS.

Methods Considering the poor prognosis and the few systemic therapeutic options, we decided to carry out a whole exome sequencing (WES) of the tumour and germline DNA.

Results WES identified a germline variation (c.1863_1864insT) in the MLH1 gene corresponding to a pathogenic mutation: (p. Leu622Serfs*10), whereas the family history did not fit with classical criteria for Lynch syndrome. Loss-of-heterozygosity at MLH1 locus was found in the tumour. Immunohistochemistry showed loss of MLH1 and PMS2 nuclear expression in the tumour cells. In view of the mismatch repair defects and a high programmed cell death ligand 1 (PD-L1) expression (60% of tumour cells expressed PD-L1), we administrated an anti-PD-1 antibody to the patient. He achieved a rapid complete response of the lung metastases, which appears sustained after a 1-year follow-up.

Conclusion This observation of an RMS revealing an unexpected Lynch syndrome underlines the overlap between tumorous and germline molecular genetics and emphasises the major impact of cancer genomic medicine in clinical practice for guiding treatment decision.

  • rhabdomyosarcoma
  • lynch syndrome
  • Mlh1
  • cancer predisposition
  • genomic medicine

https://doi.org/10.1136/jmedgenet-2018-105594

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    Footnotes

    • Contributors CT, KL, A-PG-R, AM-L, JC, HB and PL-P: have made substantial contributions to the conception and design of the work; and the acquisition, analysis and interpretation of data for the work. EP, FL, PB-R, MV and FG: have made substantial contributions to the acquisition, analysis and interpretation of data for the work.

    • Funding This work was supported by the grant EXORARE from the Cancéropôle Ile de France/INCa, by the Cancer Research for Personalized Medicine program (CARPEM). This work was supported by the Cochin Immunomodulatory Therapies Multidisciplinary Study group (CERTIM).

    • Competing interests None declared.

    • Patient consent Obtained.

    • Provenance and peer review Not commissioned; externally peer reviewed.