15283-B-Blokker

121 PM tissue biopsies obtained at MIA: an RNA-quality analysis 7 INTRODUCTION In most cancer patients, only tissues from the primary tumors are biopsied or resected for diagnostic and therapeutic purposes. Outside the context of studies clinicians do not biopsy recurrent or metastatic disease, unless it has therapeutic significance. This hampers the molecular comparison of primary and metastatic disease, despite the fact that it is now evident that there is not just intra-tumor heterogeneity 173,174 but that there are also considerable molecular differences between primary tumors and metastases. 175-178 Chemotherapeutic and other systemic treatments based on genetic characteristics of the primary tumor may not work effectively on metastases due to changes of molecular targets, such as receptor conversion. 179-181 Knowing the molecular characteristics of metastases may help to target them specifically. It is, therefore, necessary to pursue molecular research, comparing primary tumors and metastases. Post-mortem investigation is an opportunity to obtain tissue samples from (recurred) primary tumors and metastases for comparative molecular studies. 182,183 The so-called “rapid autopsy” is performed soon after death, in order to minimize post- mortem degradation of collected tumor samples and allows for procurement of among others high quality RNA. 184,185 Unfortunately, autopsies are rarely performed on patients who died of cancer. Bereaved relatives are often not willing to give their consent for conventional autopsy (CA), mainly because they feel that their loved one has suffered enough from the disease and they consider (further) mutilation of the deceased’s body undesirable. 38,40,81 Minimally invasive autopsy (MIA) may be an acceptable alternative to CA, 57 because with MIA, the body is imaged by CT and MRI and tissue samples from a (recurred) primary tumor and metastases are obtained through CT-guided biopsies, leaving the body intact. Here we have investigated RNA in such biopsies as a measure of overall quality of the tissue for molecular studies. We studied whether the biopsies yielded: a) a sufficient amount of RNA and b) RNA of sufficient quality for downstream RNA analysis. By using RNA isolated from MIA, CA and fresh frozen ex vivo tissue in a RT-qPCR amplicon size assay, we were able to determine the levels of post-mortem RNA degradation and quality.

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