A genome-wide survey of RAS transformation targets.

An important aspect of multi-step tumorigenesis is the mutational activation of genes of the RAS family, particularly in sporadic cancers of the pancreas, colon, lung and myeloid system. RAS genes encode small GTP-binding proteins that affect gene expression in a global way by acting as major switches in signal transduction processes, coupling extracellular signals with transcription factors. Oncogenic forms of RAS are locked in their active state and transduce signals essential for transformation, angiogenesis, invasion and metastasis via downstream pathways involving the RAF/MEK/ERK cascade of cytoplasmic kinases, the small GTP-binding proteins RAC and RHO, phosphatidylinositol 3-kinase and others. We have used subtractive suppression hybridization (SSH), a PCR-based cDNA subtraction technique, to contrast differential gene expression profiles in immortalized, non-tumorigenic rat embryo fibroblasts and in HRAS- transformed cells. Sequence and expression analysis of more than 1,200 subtracted cDNA fragments revealed transcriptional stimulation or repression of 104 ESTs, 45 novel sequences and 244 known genes in HRAS- transformed cells compared with normal cells. Furthermore, we identified common and distinct targets in cells transformed by mutant HRAS, KRAS and NRAS, as well as 61 putative target genes controlled by the RAF/MEK/ERK pathway in reverted cells treated with the MEK-specific inhibitor PD 98059.

[Immunothrombocytopenia of the newborn caused by platelet-specific antibodies (anti-P1A1) (author's transl)]. / Allimmunthrombozytopenipe der Neugeborenen durch thrombozytenspezifische Antikörper (Anti-P1A1).

For the first time in the German speaking area 8 cases of neonatal immunothrombocytopenia caused by platelet-specific P1A1 antibodies could be ascertained. The disease is caused by fetomaternal incompatibility against platelet antigens. All mothers were healthy. The children showed a postnatal tendency for petechial haemorrhages. Cerebral haemorrhages occurred in two cases. Optimal treatment consists of administration of P1A1-negative platelets (perhaps of the mother). Demonstration of platelet antibodies is possible nowadays by adequate serological methods.