However, SOX2 is not expressed in the β-catenin accumulating clusters in human ACP, but rather in sporadic cells within the tumour [ 17].
These cells were mostly observed as densely accumulated clusters around the pericyst in CE biopsies.
It has been observed that yeast cells accumulate clusters of mutations when treated with the DNA alkylating chemical MMS and that tumor cells accumulate clusters of mutations in a variety of contexts, some related to the action of cytosine deaminases (Nik-Zainal et al. 2012; Roberts et al. 2012; Burns et al. 2013).
This was confirmed by in situ hybridization analysis on Hesx1 Cre/ +; Ctnnb1 lox(ex3)/ + tumorigenic pituitaries, which revealed a pattern of expression of these genes in restricted focal points reminiscent of the β-catenin accumulating clusters (Fig. 5a, c, e).
Since clear cell RCCs showing a higher incidence of vascular involvement, renal vein tumor thrombi and higher pathological TNM stages were accumulated in Cluster BT, our Clusters AT and BT can be considered clinicopathologically valid.
Changes included increased lysosomal number with variable sized including many small structures, often accumulating in clusters in PPARγ-deficient mPrE cells.
These data indicated that copy number alterations, especially chromosomal gain, were accumulated in cluster A in comparison with clusters B1 and B2.
In addition, chromosomal losses tended to be accumulated in cluster B1 in comparison with clusters A and B2, although such differences did not reach statistical significance.
All 11 cluster M-specific mutations were found in at least one sample in cluster P1, and no somatic mutation was further accumulated in cluster M. In addition, SCNA showed that the genomic architecture of samples in cluster M were similar to the patterns in cluster P1.
Clinicopathologically aggressive clear cell RCCs were accumulated in Cluster BN, and the overall survival rate of patients in Cluster BN was significantly lower than that of patients in Cluster AN.
Clinicopathologically aggressive clear cell RCCs were accumulated in Cluster BT, and the overall survival rate of patients in Cluster BT was significantly lower than that of patients in Cluster AT.
