Single-nucleotide polymorphism-mass array reveals commonly deleted regions at 3p22 and 3p14.2 associate with poor clinical outcome in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common solid tumors in the world with poor prognosis. Deletion of chromosome 3p is one of the most frequent chromosomal alterations in ESCC, suggesting the existence of one or more tumor suppressor genes (TSGs) at this region. In the present study, a recently developed high-throughput and high-resolution technology, single-nucleotide polymorphism (SNP)-mass array, was applied to investigate loss of heterozygosity on 3p in 100 primary ESCC cases with 386 SNP markers. Four commonly deleted regions (CDRs) at 3p26.3, 3p22, 3p21.3 and 3p14.2 were identified. Absent and down-regulated expression of several candidate TSGs, including CHL1, PCAF, RBMS3, PLCD1 and CACNA2D3, were detected in primary ESCC tumors and ESCC cell lines. Moreover, deletions of CDRs 2 and 4 were correlated with advanced tumor stage and deletion of CDR2 was associated with tumor metastasis in ESCC. Our findings provided evidence that minimal deleted regions at 3p26.3, 3p22, 3p21.3 and 3p14.2 containing potential TSGs may contribute to the pathogenesis of esophageal cancer. © 2008 Wiley-Liss, Inc.link_to_subscribed_fulltex

A favorable outcome of advanced dermatofibrosarcoma protuberans under treatment with sunitinib after imatinib failure

Wei Xiao,1,2 Yi Que,1,2 Ruiqing Peng,1,2 Ya Ding,1,2 Jingjing Zhao,1,2 Xizhi Wen,1,2 Desheng Weng,1,2 Xiaoshi Zhang,1,2 Yuanxiang Guan,2,3,* Xing Zhang1,2,* 1Melanoma and Sarcoma Medical Oncology Unit, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors equally contributed to the work Abstract: While traditional cytotoxic agents play a limited role in advanced dermatofibrosarcoma protuberans (DFSP), the treatment of sunitinib for patients with advanced DFSP after imatinib failure is not well defined. The objective of this case report was to analyze the relationship between molecular mechanisms and clinical outcomes of sunitinib treatment in patients with advanced DFSP after imatinib failure. In this case report, a 37-year-old man suffered from advanced DFSP progression after surgical operation, microwave ablation, and chemotherapy. The immunohistochemistry in this patient revealed abundant expression of platelet-derived growth factor receptor-beta on tumor cells, which is one of the drug targets of sunitinib. The nucleotide sequence analysis revealed COL1A1-PDGFB fusion transcripts in this patient. Thus, we treated the patient with sunitinib, a multi-targeted tyrosine kinase inhibitor, after imatinib failure. After treatment with sunitinib, the patient exhibited a partial response and 9 months’ progression-free survival without significant adverse drug effects. In our case, the patient with advanced DFSP experienced a favorable outcome in 9-months’ progression-free survival and a significant improvement of quality of life without serious side effects after sunitinib treatment. Therefore, sunitinib could serve as another treatment option for patients with advanced DFSP. Keywords: COL1A1-PDGFB fusion gene, dermatofibrosarcoma protuberans, platelet-derived growth factor receptor-beta, sunitini