No evidence for PML-RARa bcr1 fusion gene in colorectal cancer
Colorectal cancer is the third most prevalent cancer and a leading cause of cancer death. Metastatic colorectal cancer patients are treated with anti-EGFR monoclonal antibodies in combination with chemotherapy; however, the efficiency is only 10-20% of such patients. An increasing amount of data has demonstrated that response to anti-EGFR therapies is confined to patients with KRAS and BRAF wild type tumors but still some of these patients are non responders to this treatment. The presence of oncogenic deregulation of different members of EGFR downstream signaling or crosstalk molecules could predict the lack of response in these patients. In this study, 40 wild type KRAS and BRAF colorectal tumors were analyzed to elucidate whether PML-RARa bcr1 fusion gene may play a role in colorectal carcinogenesis. Specifically we want to determine if this fusion could be responsible for the inability to respond to anti-EGFR monoclonal antibodies. Here, for the first time it is reported, that PML-RARa bcr1 fusion is not responsible for colorectal tumor development and also, this translocation is not predicting the lack of efficacy of anti-EGFR therapies in wild type KRAS and BRAF colorectal cancer patients. These results also suggest that PML-RARa is unlikely to be a promising target for adjuvant therapy in colorectal cancer patients.
KeywordsPML-RARa bcr1 EGFR KRAS BRAF Colorectal cancer
V-raf murine sarcoma viral oncogene homolog B1
Human homolog of the Kirsten rat sarcoma-2 virus oncogene
Epidermal grown factor
Metastatic colorectal cancer
Promyelocytic leukemia (PML) gene and retinoic acid receptor-alpha (RARa) fusion gene
Thanks to Sabrice Guerrier for his technical help. This work was supported by Junta de Castilla y León.
Conflict of interest
The author declares that she has no competing interests.
- 8.Grimwade D, Biondi A, Mozziconacci MJ et al (2000) Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): results of the European Working Party. Groupe Francais de Cytogenetique Hematologique, Groupe de Francais d’Hematologie Cellulaire, UK Cancer Cytogenetics Group and BIOMED 1 European community-concerted action molecular cytogenetic diagnosis in haematological malignancies. Blood 96:1297–1308PubMedGoogle Scholar
- 19.Vincenzi B, Santini D, Perrone G, et al (2011) PML as a potential predictive factor of oxaliplatin/fluoropyrimidine-based first line chemotherapy efficacy in colorectal cancer patients. J Cell Physiol. doi: 10.1002/jcp.22801