Other genes identified in precursor lesions include PENK, CDKN2A/p16, STK11/LKB1, SPARC, SFRP1/SARP2 (chromosome arm 8p), TSLC1, RELN (chromosome arm 7q), TFPI2, CLDN5 (chromosome arm 22q), and UCHL1 in IPMNs (37,122,123); PENK, CDKN2A/p16, CLDN5, NPTX2, RPRM, SFRP1/SARP2, and LHX1 (chromosome arm 11p) in PanINs (117,118,124); and CDKN2A/p16 in MCNs.
Differential and epigenetic gene expression profiling identifies frequent disruption of the RELN pathway in pancreatic cancers.
The most notable of the altered genes in this experiment that are associated with these functions include RELN
, a gene with multiple functions throughout early nervous system development, including a role in activating a signal cascade for regulating neuronal migration (Jossin 2004), and ROB02 [roundabout, axon guidance receptor, homolog 2 (Drosophila)], a gene that activates a repulsive guidance signal for neurons (Lopez-Bendito et al.
Table 2 classifies the 68 up-regulated and 39 down-regulated genes into 9 classes according to their known functions and reports the genes mainly involved in detoxication/ chemoresistance (ABCB1), invasiveness and cell adhesion pathways (ENPP2, EMP2, DCN), and neuronal structure and signaling (PRPH, RELN
, SYCP2, MDK).