Additionally, as a further validation of our observations, Gene Set Enrichment Analysis (GSEA) was employed to identify differences in gene expression profiles from tumors arising in women aged ≤45 years (class 1) and ≥65 years (class 2), thus validating the above findings [17].
Their participation contributed to effective engagement of our study population and to validation of study observations.
We agree that in vivo validation of our observations in MEPMs is highly desirable.
'Adaptive' trial format design, favouring fast and easy validation of clinical observations in the laboratory as well as streamlining of experimental information from bench-to-bedside.
Validation of these observations by direct sequencing and follow-up functional analyses of candidate primate-specific and human-specific regulatory sequences will be required.
As a result of standardization, the availability of large numbers of data sets describing the transcriptional behavior of breast cancers has permitted the validation of local observations in silico.
Further validation of these observations in a wider range of cell lines and in orthotopic models are required before a clinical evaluation of AG-014699 in combination with temozolomide for intra-cranial malignancies would be indicated.
The development of Cre drivers more precise than the Wnt1-Cre that drive recombination within the secondary palate itself (rather than in the early neural crest) would facilitate the in vivo validation of the observations made in MEPMs.
