Recent studies using whole-exome sequencing and/or targeted sequencing of UTUC samples identified recurrent mutations of genes known to be altered in bladder carcinomas, although with different frequencies (e.g., HRAS). While genome-wide genetic alterations of muscle-invasive bladder carcinomas have been extensively studied by The Cancer Genome Atlas (TCGA) project and others, genetic alterations occurring in UTUC are limited. Such differences might dictate whether patients with UTUC display a higher incidence of invasive disease at diagnosis as compared to patients with bladder carcinomas. Upper tract urothelial carcinomas represent 5–10% among all urothelial carcinomas, and they can arise within the ureter or the renal pelvis, which are derived from different embryonic tissues as compared to the bladder urothelium. NMI tumors are costly to treat as they often recur, and 10–15% of those patients progress to an MI state. NMI represents 75% of tumors, while MI represents the latter 25%. Urothelial carcinoma is considered the fifth most common cancer in Western countries, and it is divided at the pathological level into two groups: non-muscle-invasive (NMI) and muscle-invasive (MI) tumors, according to the level of invasion of the detrusor muscle. Our study delineates for the first time the key role for convergence between genetic and epigenetic alterations in shaping clinicopathological and immune upper tract urothelial carcinoma features. While the former is hypomethylated, immune-depleted, and enriched for FGFR3-mutated, the latter is hypermethylated, immune-infiltrated, and tightly associated with somatic mutations of SWI/SNF genes. Unsupervised DNA methylation subtype classification identifies two epi-clusters associated with distinct muscle-invasive status and patient outcome, namely, EpiC-low and EpiC-high. Overall, mutations of ZFP36 family genes ( ZFP36, ZFP36L1, and ZFP36L2) are identified in 26.7% of cases, which display a high mutational load. In addition to mutations of FGFR3 and KDM6A, we identify ZFP36L1 as a novel, significantly mutated tumor suppressor gene. We perform an integrative genome- and methylome-wide profiling of diverse non-muscle-invasive and muscle-invasive upper tract urothelial carcinomas. Their classic Frontier Burger is nestled between soft bread is a 1/2 lb Black Angus beef patty joined by “the works” – lettuce, tomato, onion, pickle, and burger sauce. Try this burger on National Burger Day for only $15.Crosstalk between genetic, epigenetic, and immune alterations in upper tract urothelial carcinomas and their role in shaping muscle invasiveness and patient outcome are poorly understood. To add a Peruvian spin on this burger, chimichurri and rocoto cream also joins the mix. Only available on their brunch menu and for only $18, a grass-fed beef patty is accompanied by bacon, fried egg, and oozing cheese. Grand Ave) the early diners can select their A Lo Pobre Burger. The early bird may get the worm, but at Tanta Chicago (118 W. Big Macs are synonymous with playing baseball for me.” The only fast food restaurant at the time close to where I lived was McDonald’s so we would always have Big Macs. When asked about the inspiration of the Mordecai Burger, or as nicknamed by Mordecai’s Executive Chef Michael McKinnell, the “fancy Big Mac,” McKinnell shares, “Growing up, my father would always take me out to eat after my little league games. Served with a side of crispy fries for only $20. Mordecai also offers the opportunity to add egg and bacon. Blanketing the beef is artisan American cheese directly from Cooper Cheese, providing a flavor that balances with the added shredded lettuce, diced onion, and house aioli. Clark St), their burger’s double patty is sourced from Central Illinois’ Slagle Family Farm. Confit onion, American cheese, dijonnaise, and house pickles are then stacked and pressed between a soft brioche bun.Īt Mordecai Chicago (3632 N. Here, two juicy 4oz patties are joined with thick cut bacon. Randolph St) is serving up their $20 Le Cheeseburger Royale.
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