Delineation of the infrequent mosaicism of KRAS mutational status in metastatic colorectal adenocarcinomas
- Céline Bossard1,
- Sébastien Küry1,
- Philippe Jamet2,
- Hélène Senellart3,
- Fabrice Airaud1,
- Jean-François Ramée4,
- Stéphane Bézieau1,
- Tamara Matysiak-Budnik1,2,
- Christian L Laboisse1,
- Jean-François Mosnier1
- 1Université de Nantes, Faculté de Médecine de Nantes, EA 4273 Biometadys, Nantes, France
- 2Institut des Maladies de l'Appareil Digestif et Service d'Hépato-Gastroentérologie, CHU de Nantes, France
- 3Centre de Lutte contre le Cancer Nantes Atlantique, Service d'Oncologie Médicale, Nantes, France
- 4Centre Catherine De Sienne, Service d'Oncologie Médicale, Nantes, France
- Correspondence to Dr Céline Bossard, CHU Nantes, Service d'Anatomie et Cytologie Pathologiques, EA 4273 Biométadys, Université de Nantes, Faculté de Médecine, 1 rue Gaston Veil, Nantes 44035, France;
Contributors All authors have contributed substantially to this work. They have read and approved this manuscript.
- Accepted 23 December 2011
- Published Online First 18 January 2012
This study addresses the extent of the heterogeneity of KRAS status, present in a minority of metastatic colorectal carcinomas (mCRCs), on the basis of a thorough analysis of surgical resection specimens. Eighteen patients with mCRC were included. KRAS mutations (exon 2, codons 12 and 13) were determined using PCR and subsequent direct sequencing. This analysis included primary tumours (n=21), synchronous (n=10) and metachronous (n=18) matched metastases, and pelvic recurrence (n=1). Heterogeneity of KRAS status consisted in KRAS mutated in (i) the primary tumour but not in its synchronous metastasis, (ii) the metastasis but not in the primary tumour, (iii) the pelvic recurrence but not in the primary tumour, (iiii) some metastases and not in others from the same patient. Finally, the KRAS status varied among different areas of the same metastatic focus. This study defines the concept of KRAS mosaicism that affects a minority of mCRCs.
- Metastatic colorectal cancer
- KRAS mutation mosaicism
- cancer genetics
- colorectal cancer
- inflammatory bowel disease
- molecular genetics
- diagnostic screening
Funding This study was supported in part by a grant from a Projet Hospitalier de Recherche Clinique (BRD/05/10/C).
Competing interests None.
Patient consent Each patient signed a local written informed consent.
Ethics approval Scientific committee of the Tumorothèque Nantes Atlantique.
Provenance and peer review Not commissioned; externally peer reviewed.