Novel mechanistic insights into ectodomain shedding of EGFR Ligands Amphiregulin and TGF-α: impact on gastrointestinal cancers driven by secondary bile acids.
Cancer data from 1980 to 2007 were obtained from the Familial Gastrointestinal Cancer Registry in Toronto for 321 persons with known MMR mutations: mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1); mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2); mutS homolog 6 (E. coli) (MSH6); and PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2).
Given recent reports of TKI-responsive cases of esophageal and pancreatic cancer, this study was designed to determine the prevalence of EGFR mutations in these gastrointestinal cancers.
Although SMAD4 has been established as a tumor suppressor gene somatically mutated in pancreatic, gastrointestinal, and skin cancers, and germline loss-of-function lesions and deletions of this gene have been documented to cause disorders that predispose individuals to gastrointestinal cancer and vascular dysplasias, the present report identifies a previously unrecognized class of mutations in the gene with profound impact on development and growth.
The identification of SMAD4 mutations in HHT patients without prior diagnosis of JP has significant and immediate clinical implications, as these people are likely to be at risk of having JP-HHT with the associated increased risk of gastrointestinal cancer.
Any JP patient with a SMAD4 mutation is, therefore, at risk for the visceral manifestations of HHT and any HHT patient with SMAD4 mutation is at risk for early onset gastrointestinal cancer.
Unlike the high incidences of Smad4 mutation or deletion in pancreatic cancer and gastrointestinal cancers, Smad4 gene is seldom mutated or deleted in hepatocellular carcinoma (HCC).
At the 2013 World Congress on Gastrointestinal Cancers, investigators have recently dealt with many clinically relevant questions, such as the preferred biologic drug to be used upfront in patients with KRAS wild-type colorectal tumors, the optimal treatment intensity, the most suitable maintenance strategy, the need for deeper molecular information when using EGFR inhibitors and the use of antiangiogenic drugs in the elderly.
The intratumoural immune cell subsets (CD4, CD8, Foxp3), the expression of immune checkpoints (PD-1, PD-L1), the defect in mismatch repair proteins and the mutation analysis of multiple clinically relevant genes in the gastrointestinal cancer setting were also determined.
Thymidylate synthase (TS), Dihydropyrimidine dehydrogenase (DPD) and Thymidine Phosphorylase (TP) gene expressions are reported to be predictive markers for 5-fluorouracil (5-FU) sensitivity in gastrointestinal cancer.
Ongoing studies at the Hereditary Gastrointestinal Cancer Registry in Hong Kong have revealed a unique germline MSH2c.1452-1455delAATG mutation that has not been reported in other ethnic groups.
Thymidylate synthase (TS), Dihydropyrimidine dehydrogenase (DPD) and Thymidine Phosphorylase (TP) gene expressions are reported to be predictive markers for 5-fluorouracil (5-FU) sensitivity in gastrointestinal cancer.
PLC-ε1 gene polymorphisms significantly enhance the risk of esophageal squamous cell carcinoma in individuals with a family history of upper gastrointestinal cancers.
Here, the prevalence of the single nucleotide polymorphisms (SNPs) rs6214 in the IGF type I (IGF-I) gene and rs6898743 in the growth hormone receptor (GHR) gene in patients with GI cancer and controls was studied.