Invertebrate p53-like mRNA isoforms are differentially expressed in mussel haemic neoplasia

Mussels of the genus Mytilus are widely used in environmental monitoring. They can develop a leukaemia-like disease, haemic neoplasia, which could be induced, in part, by environmental stressors. The molluscan p53 tumor suppressor gene family was previously shown to be involved in haemic neoplasia at the protein level. The purpose of this study was the quantification of molluscan p53-like isoforms at the mRNA level in mussels with haemic neoplasia compared to normal controls. The three isoforms monitored were a p53-like, a TAp63/73-like containing an intact transactivation (TA) domain, and an NH(2)-terminally truncated p63/73 isoform termed DeltaNp63/p73-like that lacks the full TA domain. Using a comprehensive data set of 62 individual Mytilus trossulus and reverse transcription real-time PCR, we found that both the p53 and the DeltaNp63/73 isoforms were up-regulated in neoplastic haemocytes compared to normal haemocytes (p<0.0001). In contrast, the mRNA levels of the non-truncated isoform TAp63/73 did not change significantly in mussels with the disease at alpha=0.01 (p=0.0141), in contrast to previous findings at the protein level. Correlations in mRNA levels between the truncated isoform and the full-length isoforms in normal haemocytes were lost in neoplastic haemocytes. The increase in mRNA concentration of the truncated DeltaNp63/73 isoform in molluscan haemic neoplasia is similar to observations in many human cancers and cell lines and underlines the phylogenetically ancient oncogenic role of this isoform.