Genomic and Functional Approaches to Understanding Cancer Aneuploidy

Pan-cancer computational histopathology reveals mutations, tumor composition and prognosis

“…Another recurrent class of alterations are arm-level copy number alterations. We performed regularised multinomial regression on the copy number status of 17 whole chromosome and 39 arm-level gains and losses 17 . In total, 105 out of 410 gain:cancer pairs and 167 out of 570 loss:cancer pairs (with at least 10 altered samples) showed a measurable association with image features (AUC > 0.5 with 95% CI, Figure 2a, Supplementary Table 2 ).…”

“…Whole genome doubling (WGD) status were called using the criteria described previously 54 . Chromosome and chromosome arm level gains and losses were retrieved from 17 . Focal amplifications and deletions were defined for regions retrieved from 18 .…”

Single chromosome gains can function as metastasis suppressors and metastasis promoters in colon cancer

“…In contrast, a Z score less than −1.96 indicates that a chromosome gain event is significantly associated with patient survival (or that a chromosome loss event is associated with death). 10,133 of these patients' tumors have been analyzed by SNP-chip, allowing their tumors' bulk karyotype to be determined (Taylor et al 2018). Tumors in the TCGA lack comprehensive annotation of metastases, so we instead used either "overall survival" or "progression-free survival" as clinical endpoints for this analysis (Table S3A, and see the Materials and Methods).…”

“…Unpaired t-test * p<0.05; ** p<0.005 *** p<0.0005. Scale bar, 30 and 50 µm (A) The total number of aneuploid chromosomes in each tumor was calculated according to (Taylor et al 2018). In each cancer type, patients were subdivided into two groups: low aneuploidy (≤ 20 th percentile aneuploidy score) and high aneuploidy (≥ 80 th percentile aneuploidy score).…”

Gene networks in cancer are biased by aneuploidies and sample impurities

“…hence correlation that has so far not been discussed in depth. For instance, cancer cells often harbor copy number changes ranging from small segments (focal CNAs) up to the level of whole chromosomes (aneuploidies) 54 . Gene expression has been shown to follow these copy number changes 26,55,56 , whereas protein expression is often compensated for 57 .…”