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


Journal

Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R

Informations de publication

Date de publication:
02 2020
Historique:
received: 08 07 2018
revised: 26 09 2018
accepted: 04 10 2018
pubmed: 26 10 2018
medline: 3 2 2021
entrez: 25 10 2018
Statut: ppublish

Résumé

Rhabdomyosarcoma (RMS) is rare cancer affecting children and adults. Pleomorphic RMS histology is almost exclusive to adult patients and often resistant to chemotherapy. We report the case of a 19-year-old patient who presented with a metastatic chemoresistant pleomorphic RMS. 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. WES identified a germline variation (c.1863_1864insT) in the 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.

Sections du résumé

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
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.

Identifiants

pubmed: 30352869
pii: jmedgenet-2018-105594
doi: 10.1136/jmedgenet-2018-105594
doi:

Substances chimiques

Antibodies, Anti-Idiotypic 0
B7-H1 Antigen 0
Biomarkers, Tumor 0
CD274 protein, human 0
MLH1 protein, human 0
PMS2 protein, human EC 3.6.1.-
Mismatch Repair Endonuclease PMS2 EC 3.6.1.3
MutL Protein Homolog 1 EC 3.6.1.3

Types de publication

Case Reports Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

104-108

Informations de copyright

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Camille Tlemsani (C)

Service de Génétique et Biologie Moléculaires, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris, France.
Service d'Oncologie Médicale, Sarcoma center, Netsarc National Network, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris, France.
EA7331, Université Paris Descartes, Faculté de Pharmacie de Paris, Paris, France.

Karen Leroy (K)

Service de Génétique et Biologie Moléculaires, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris, France.
Faculté de médecine, Université Paris Descartes, Paris, France.

Anne-Paule Gimenez-Roqueplo (AP)

Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France.
INSERM UMR-970, Paris Cardiovascular Research Center, Paris, France.

Audrey Mansuet-Lupo (A)

Faculté de médecine, Université Paris Descartes, Paris, France.
Service d'Anatomopathologie, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Assistance Publique Hôpitaux de Paris, Paris, France.

Eric Pasmant (E)

Service de Génétique et Biologie Moléculaires, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris, France.
EA7331, Université Paris Descartes, Faculté de Pharmacie de Paris, Paris, France.

Frederique Larousserie (F)

Faculté de médecine, Université Paris Descartes, Paris, France.
Service d'Anatomopathologie, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Assistance Publique Hôpitaux de Paris, Paris, France.

Pascaline Boudou-Rouquette (P)

Service d'Oncologie Médicale, Sarcoma center, Netsarc National Network, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris, France.
Faculté de médecine, Université Paris Descartes, Paris, France.

Michel Vidaud (M)

Service de Génétique et Biologie Moléculaires, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris, France.
EA7331, Université Paris Descartes, Faculté de Pharmacie de Paris, Paris, France.

Jacques Cadranel (J)

Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Service de Pneumologie and Sorbonne Université, Paris, France.

Helene Blons (H)

INSERM UMR-S1147, Université Sorbonne-Paris-Cité, Paris, France.
Service de Biochimie, Pharmacologie et Biologie Moléculaire, Hôpital Européen Georges-Pompidou, Assistance Publique Hôpitaux de Paris, Paris, France.

Francois Goldwasser (F)

Service d'Oncologie Médicale, Sarcoma center, Netsarc National Network, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris, France.
Faculté de médecine, Université Paris Descartes, Paris, France.

Pierre Laurent-Puig (P)

Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France.
INSERM UMR-S1147, Université Sorbonne-Paris-Cité, Paris, France.

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Classifications MeSH