Rational testing for gene fusion in colorectal cancer: MSI and RAS-BRAF wild-type metastatic colorectal cancer as target population for systematic screening

Matthieu Delaye; Sabrina Ibadioune; Catherine Julié; Cristi Marin; Frédérique Peschaud; Renato Lupinacci; Sophie Vacher; Ladidi Ahmanache; Samantha Antonio; Anne Schnitzler; Bruno Buecher; Pascale Mariani; Yves Allory; Olfa T Grati; Jean F Emile; Cindy Neuzillet; Ivan Bièche

doi:10.1016/j.ejca.2022.04.024

Rational testing for gene fusion in colorectal cancer: MSI and RAS-BRAF wild-type metastatic colorectal cancer as target population for systematic screening

Eur J Cancer. 2022 Jul:170:85-90. doi: 10.1016/j.ejca.2022.04.024. Epub 2022 May 19.

Authors

Matthieu Delaye¹, Sabrina Ibadioune², Catherine Julié³, Cristi Marin³, Frédérique Peschaud⁴, Renato Lupinacci⁴, Sophie Vacher², Ladidi Ahmanache², Samantha Antonio², Anne Schnitzler², Bruno Buecher⁵, Pascale Mariani⁶, Yves Allory⁷, Olfa T Grati², Jean F Emile³, Cindy Neuzillet⁸, Ivan Bièche⁹

Affiliations

¹ Department of Medical Oncology, Curie Institute, Versailles Saint-Quentin University, Paris Saclay University, Saint-Cloud, France.
² Department of Genetics, Institut Curie, Paris University, Paris, France.
³ Université Paris-Saclay, Université de Versailles SQY (UVSQ), EA4340-BECCOH, Assistance Publique-Hôpitaux de Paris (AP-HP), Ambroise-Paré Hospital, Smart Imaging, Service de Pathologie, Boulogne, France.
⁴ Department of Digestive and Oncologic Surgery, Ambroise Paré Hospital, Versailles Saint-Quentin University, Paris Saclay University, Boulogne-Billancourt, France.
⁵ Department of Oncogenetics, Institut Curie, Paris University, Paris, France.
⁶ Department of Surgery, Institut Curie, Paris University, Paris, France.
⁷ Department of Pathology, Hôpital Foch, Suresnes, France, Department of Pathology, Institut Curie, Saint-Cloud, France, Université Paris-Saclay, Versailles Saint-Quentin University.
⁸ Department of Medical Oncology, Curie Institute, Versailles Saint-Quentin University, Paris Saclay University, Saint-Cloud, France. Electronic address: [email protected].
⁹ Department of Genetics, Institut Curie, Paris University, Paris, France; INSERM U1016 Research Unit, Cochin Institute, Paris, France.

PMID: 35598360
DOI: 10.1016/j.ejca.2022.04.024

Abstract

Gene fusions provide access to new therapeutic opportunities for patients treated for a colorectal cancer (CRC). However, they do not excess 1% of patients. A better identification of patients in whom gene fusions are highly prevalent is a major issue in a therapeutic and medico-economics perspective. This study assesses the rates of gene fusions in CRC patients with MSI/RAS-BRAF^WT in our routine practice detected with a commercially available NGS-based fusion panel. Among the 130 MSI CRC tumors, 43 (33%) were KRAS-NRAS-BRAF^WT. A gene fusion was detected in 7 (25.9%) of the 27 MSI/RAS-BRAF^WT samples, which had RNA suitable for analysis after quality control. These fusions involved mainly NTRK1/3 (n = 5), as well as ALK (n = 1) and BRAF (n = 1). In the present study, we confirm that patients with MSI/RAS-BRAF^WT CRCs represent a subpopulation in which targetable gene fusions are overrepresented. Our results support the use of a two-step algorithm for molecular screening, in which metastatic CRC patients would have routine MSI and RAS/BRAF testing, and then only those with MSI/RAS-BRAFWT would be screened with dedicated NGS RNA panel for gene fusions.

Keywords: Colorectal cancer; Gene fusion; Medico-economics; Targeted therapy.

MeSH terms

Colorectal Neoplasms* / pathology
Early Detection of Cancer*
Gene Fusion
Humans
Microsatellite Instability
Mutation
Proto-Oncogene Proteins B-raf / genetics
Proto-Oncogene Proteins p21(ras) / genetics
RNA

Substances

RNA
BRAF protein, human
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins p21(ras)