Research Report 2010 - MDC

Graduate StudentsÖzlem Akilli ÖztürkLiang Fang*Tamara GrigoryanRitesh Gupta*Julian HeubergerJingjing Qi*Peter WendRegina WilleckeTechnical AssistantsChris Eckert*Lysann Hinz*Frauke KoselMarion MüllerSandra Rohrmoser*Simone SteinRegina VogelSecretariatIrmgard Wiznerowicz*part of the period reportedA colorectal cancer expression profile that includes transforminggrowthfactor beta inhibitor BAMBI predicts metastatic potential(A) Mean expression levels of 115 signature genes that distinguishmetastatic from non-metastatic primary tumors. Hierarchical clusteringdendrogram is shown on top: average gene expression levels inmetastatic (mPT) and non-metastatic (nPT) primary tumors (insideblack box), lymph node (LN), liver (Hep) and lung (Pul) metastases andnormal tissue (N). Selected genes that are involved in signal transduction,gene transcription or metastasis are indicated. (B) Kaplan-Meiersurvival analysis of patients from an independent cohort (50 primarytumors), as determined by quantitative RT-PCR. All patients were freeof distant metastasis at the time of sample collection.Much is known about the genes and mutations thatcause colorectal cancer (CRC), yet only a few have beenassociated with CRC metastasis. Mutations of genes ofthe Wnt/β-catenin pathway are responsible for thegeneration of over 90 % of CRC. We performed expressionprofiling experiments to identify genetic markersof risk and to elucidate the molecular mechanisms ofCRC metastasis. We compared gene expression patternsbetween metastatic and non-metastatic, stagematchedhuman colorectal carcinomas. We establisheda signature of 115 genes that differentiated metastaticfrom non-metastatic primary tumors. Among these,the TGFβ inhibitor BAMBI was highly expressed in abouthalf of metastatic primary tumors and metastases butnot in non-metastatic tumors. We have identifiedBAMBI as a target of canonical Wnt signaling thatinvolves the β-catenin co-activator BCL9-2. We observedan inverse correlation between level of BAMBI expres-Cancer Research 83