GEITP is BAA-AA-AA-AA-AA-AA-AACK. After a long, arduous five-week exhausting journey, we will now begin to resume for 2o17.
This first topic [attached] is relevant to me –– because, within recent weeks, I’ve had discussions with a colleague about whether each cancerous tumor, as it develops and progresses, is unique to that patient and to that tumor. Or if there are “predictable patterns” that are seen in all tumors of a certain type –– independent of patient (host) in which the cancer is growing. It turns out that the answer is: “somewhere in between these two hypotheses.”
Attached are two articles, combined in one file. The first article is about esophageal squamous cell carcinoma (ESCC), among the most common malignancies. Authors examined the intratumoral heterogeneity (ITH) as a function of location within the tumor, and the time during which it develops and progresses. To address this, authors performed multi-region whole-exome sequencing on 51 tumor regions from 13 ESCC cases. They also studied multi-region global-methylation profiling in three of these 13 cases. They found, an average, 35.8% show heterogeneous somatic mutations with strong evidence of ITH.
Half of the driver-mutations, located on the branches of tumor phylo-genetic trees, targeted several oncogenes –– including PIK3CA, NFE2L2 and MTOR, among others. In contrast, the majority of truncal and clonal driver-mutations occurred in tumor-suppressor genes –– including TP53, KMT2D and ZNF750, among others. Interestingly, phylo-epigenetic trees robustly recapitulated the topological structures of the phylo-genetic trees, strongly implicating a possible relationship between genetic and epigenetic alterations.
The second article is about oral cavity- and pharyngeal-cancers. Performing genome-wide association studiees (GWAS) in 6,034 cases and 6,585 controls –– from Europe, North America and South America –– authors detected eight significantly associated loci (P <5.0 x 10–8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (HLA-DQB1), 10q26.13 (LHPP) and 11p15.4 (OR52N2–TRIM5). Oral cancer was also associated with two new regions –– 2p23.3 (GPN1) and 9q34.12 (LAMC3), and with well known cancer-related loci –– 9p21.3 (CDKN2B-AS1) and 5p15.33 (CLPTM1L).
Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) Chr 6 region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*13:01–HLA-DQA1*01:03–HLA-DQB1*06:03 (odds ratio (OR) = 0.59, P = 2.7 × 10–9). Stratified analyses on a subgroup of oropharyngeal cases –– having information available on human papillomavirus (HPV) status –– indicated that this association with the class II haplotype was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10–6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.
Nat Genet Dec 2o16; 48: 1490-1499 and 1500–1507 [2 articles]