Abnormalities of the ARF-p53 pathway in primary angiosarcomas of the liver

Active TGF-β signaling and decreased expression of PTEN separates angiosarcoma of bone from its soft tissue counterpart

“…To date, few studies have reported the possible role of CDKN2A and TP53 in tumor development in a subset of angiosarcomas of soft tissue. [15][16][17][18][19][20]37,[40][41][42] Recently, it has been shown that Ink4/Arf deficiency in mice is associated with the development of angiosarcoma, lymphoma and fibrosarcoma. 43 By global testing, we demonstrate that the TGF-b pathway (TGF-b1/phospho-Smad2/PAI-1) is highly active in angiosarcoma of bone and therefore could have an important role in tumorigenesis.…”

Clinical and Molecular Biology of Angiosarcoma

“…Mutations in p53 codons 141 and 136 were identified in a small cohort of hepatic AS (Soini et al 1995) and mutations in p53 codons 249 and 255 have been associated with vinyl chloride exposure (Hollstein et al 1994). Other studies indicate the INK4a-ARF locus is frequently inactivated in liver AS independent of p53 mutations (Weihrauch et al 2002). Mutations in the PTEN tumor suppressor have also been identified in hepatic AS; an exon 7 mutation codes for a premature stop codon resulting in a nonfunctional protein (Tate et al 2007).…”

“…Activating mutations in key signaling molecules promote AS tumorigenesis. K-Ras2 mutations have been associated with AS (Marion 2005;Przygodzki et al 1997) and have been detected in hepatic AS after exposure to vinyl chloride (Weihrauch et al 2002). Ten percent of AS tumors showed activating KDR (VEGFR2) mutations (Antonescu et al 2009).…”

CpG Island Methylation Is Responsible for p14ARF Inactivation and Inversely Correlates with p53 Overexpression in Resected Non–Small Cell Lung Cancer

“…5ЈCpG hypermethylation that leads to gene silencing of the p14ARF has been described in bladder, colorectal, hepatocellular, and gastric cancers in the range of 17-35% (22,(25)(26)(27), but reports are quite limited regarding primary lung cancers. The frequency of 5ЈCpG hypermethylation of the p14ARF gene reported in this study was 30% (27 of 91) by the RE-PCR assay.…”