Evidence that the biased CIS targets form part of a larger progression network under selection was provided by KEGG pathway analysis which showed that some of the most frequent CIS targets (e.g. Ccnd3, Ccr7, Pik3cd, Pik3r5, Rasgrp1) map to metanodes that include many of the less frequent targets (Figure S4). The gene discussed is RASGRP1; the disease is in situ carcinoma.