Therefore, we developed a method for stratification of data and evaluated the method using previously characterized cases.
The previously characterized cases of DC (due to mutations in DKC1, TERC, TERT, NOP10, NHP2 and TINF2) are associated with short telomeres (as demonstrated in Fig. 4B, DKC1 lengths).
However, this value is similar to that reported in a series of previously characterized PCM cases in our laboratory [ 23].
In previously characterized DC and HHS cases, reduced telomerase activity resulted in accelerated telomere shortening to a critical length, which in turn activated DDR.
In both cases, previously characterized strong promoters were selected to drive expression of the CRISPR/Cas elements, along with widely used terminators from phages fd, λ, and T7.
For sporadic cases, previously characterized for MSI, the presence of known hereditary cancer syndromes was excluded; (IV) 23 microsatellite stability (MSS) CRCs from patients younger than 40 years (early-onset colorectal cancer with microsatellite stability: EO-MSS) recruited through the specialized Colorectal Cancer Registry of Modena in the period 1984 2008.
Most SNPs matched the expected positions (previously characterized), although in a few cases additional SNPs were also segregating.
Second, recent studies of de novo mutations suggested that they were novel and not previously characterized; this was not the case here and in fact these variants have been characterized as being common (MAF >5%) based upon HapMap allele frequencies.
Most cases have been previously characterized for status of CIMP, MSI, KRAS, and BRAF [ 23, 26, 36].
In each case we had previously characterized the curve to reach a target as the shortest-distance path with respect to a task-dependent Riemannian distance metric.
All cases and controls were previously characterized in terms of histology, DNA quality, HIV serology, and cutaneous and mucosal HPV DNA positivity [ 7, 29].
