BACKGROUND & AIMS: Mutations in TP53, a tumor suppressor gene, are associated with prognosis of many cancers. However, the prognostic values of TP53 mutation sites are not known for patients with hepatocellular carcinoma (HCC) because of heterogeneity in their geographic and etiologic backgrounds. METHODS: TP53 mutations were investigated in a total of 409 HCC patients, including Chinese (n = 336) and white (n = 73) patients, using the direct sequencing method. RESULTS: A total of 125 TP53 mutations were found in Chinese patients with HCC (37.2%). HCC patients with TP53 mutations had a shorter overall survival time compared with patients with wild-type TP53 (hazard ratio [HR], 1.86; 95% confidence interval [CI]: 1.37-2.52; P < .001). The hot spot mutations R249S and V157F were significantly associated with worse prognosis in univariate (HR, 2.11; 95% CI: 1.51-2.94; P < .001) and multivariate analyses (HR, 1.79; 95% CI: 1.29-2.51; P < .001). Gene expression analysis revealed the existence of stem cell-like traits in tumors with TP53 mutations. These findings were validated in breast and lung tumor samples with TP53 mutations. CONCLUSIONS: TP53 mutations, particularly the hot spot mutations R249S and V157F, are associated with poor prognosis for patients with HCC. The acquisition of stem cell-like gene expression traits might contribute to the aggressive behavior of tumors with TP53 mutation.
BACKGROUND & AIMS: Mutations in TP53, a tumor suppressor gene, are associated with prognosis of many cancers. However, the prognostic values of TP53 mutation sites are not known for patients with hepatocellular carcinoma (HCC) because of heterogeneity in their geographic and etiologic backgrounds. METHODS:TP53 mutations were investigated in a total of 409 HCCpatients, including Chinese (n = 336) and white (n = 73) patients, using the direct sequencing method. RESULTS: A total of 125 TP53 mutations were found in Chinese patients with HCC (37.2%). HCCpatients with TP53 mutations had a shorter overall survival time compared with patients with wild-type TP53 (hazard ratio [HR], 1.86; 95% confidence interval [CI]: 1.37-2.52; P < .001). The hot spot mutations R249S and V157F were significantly associated with worse prognosis in univariate (HR, 2.11; 95% CI: 1.51-2.94; P < .001) and multivariate analyses (HR, 1.79; 95% CI: 1.29-2.51; P < .001). Gene expression analysis revealed the existence of stem cell-like traits in tumors with TP53 mutations. These findings were validated in breast and lung tumor samples with TP53 mutations. CONCLUSIONS:TP53 mutations, particularly the hot spot mutations R249S and V157F, are associated with poor prognosis for patients with HCC. The acquisition of stem cell-like gene expression traits might contribute to the aggressive behavior of tumors with TP53 mutation.
Authors: Petko M Petkov; Jiri Zavadil; David Goetz; Tearina Chu; Robert Carver; Charles E Rogler; Erwin P Bottinger; David A Shafritz; Mariana D Dabeva Journal: Hepatology Date: 2004-03 Impact factor: 17.425
Authors: K Honda; E Sbisà; A Tullo; P A Papeo; C Saccone; S Poole; M Pignatelli; R R Mitry; S Ding; A Isla; A Davies; N A Habib Journal: Br J Cancer Date: 1998-03 Impact factor: 7.640
Authors: Frank Staib; Markus Krupp; Thorsten Maass; Timo Itzel; Arndt Weinmann; Ju-Seog Lee; Bertil Schmidt; Martina Müller; Snorri S Thorgeirsson; Peter R Galle; Andreas Teufel Journal: Liver Int Date: 2013-09-09 Impact factor: 5.828
Authors: Jingjing Jiao; Weibo Niu; Ying Wang; Keith Baggerly; Yuanqing Ye; Xifeng Wu; Dewitt Davenport; Jose Luis Almeda; Monica M Betancourt-Garcia; R Armour Forse; Heather L Stevenson; Gordon P Watt; Joseph B McCormick; Susan P Fisher-Hoch; Laura Beretta Journal: Cancer Prev Res (Phila) Date: 2017-10-31