INTRODUCTION: Translocations of anaplastic lymphoma kinase (ALK) to various fusions partners and formation of oncogenic fusions proteins have been demonstrated in a variety of human malignancies. These fusion-proteins are potential pharmaceutically targets. Aim of this study was to investigate ALK gene status in a large cohort of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the oesophagus. MATERIALS AND METHODS: 117 SCCs and 136 ACs were included into this study. ALK and EML4 gene status were evaluated by fluorescence in situ hybridisation (FISH) using a triple colour break apart single fusion probe and a probe against 2p11. ALK and EML4 protein expression was determined by immunohistochemistry. Data on expression of ALK downstream effector tyrosine-705 phosphorylated STAT3 (pSTAT3) were available from a previous study. RESULTS: FISH was performed successfully in 251 cases. All cases were negative for ALK translocations, while 14/135 (12.1%) of SCCs and 14/116 (10.4%) of ACs showed ALK amplifications. Concomitant EML4 amplifications were present in 27/28 cases with ALK amplifications. Three cases (two SCC, one with additional ALK &EML4 amplification and one AC) showed EML4 translocations not involving ALK. None of the tumours with ALK amplification showed ALK protein expression, and no correlation with clinical parameters, survival or pSTAT3 expression was observed. CONCLUSIONS: While ALK translocations are not present in oesophageal cancer, ALK amplifications are common events with comparable rates in SCC and AC. Since ALK amplified breast cancer cells were shown to respond to ALK inhibitors, ALK amplified oesophageal cancers might be considered as possible candidates for therapies targeting ALK.
INTRODUCTION: Translocations of anaplastic lymphoma kinase (ALK) to various fusions partners and formation of oncogenic fusions proteins have been demonstrated in a variety of humanmalignancies. These fusion-proteins are potential pharmaceutically targets. Aim of this study was to investigate ALK gene status in a large cohort of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the oesophagus. MATERIALS AND METHODS: 117 SCCs and 136 ACs were included into this study. ALK and EML4 gene status were evaluated by fluorescence in situ hybridisation (FISH) using a triple colour break apart single fusion probe and a probe against 2p11. ALK and EML4 protein expression was determined by immunohistochemistry. Data on expression of ALK downstream effector tyrosine-705 phosphorylated STAT3 (pSTAT3) were available from a previous study. RESULTS: FISH was performed successfully in 251 cases. All cases were negative for ALK translocations, while 14/135 (12.1%) of SCCs and 14/116 (10.4%) of ACs showed ALK amplifications. Concomitant EML4 amplifications were present in 27/28 cases with ALK amplifications. Three cases (two SCC, one with additional ALK &EML4 amplification and one AC) showed EML4 translocations not involving ALK. None of the tumours with ALK amplification showed ALK protein expression, and no correlation with clinical parameters, survival or pSTAT3 expression was observed. CONCLUSIONS: While ALK translocations are not present in oesophageal cancer, ALK amplifications are common events with comparable rates in SCC and AC. Since ALK amplified breast cancer cells were shown to respond to ALK inhibitors, ALK amplified oesophageal cancers might be considered as possible candidates for therapies targeting ALK.
Authors: Min Hwan Kim; Soohyeon Lee; Ja Seung Koo; Kyung Hae Jung; In Hae Park; Joon Jeong; Seung Il Kim; Seho Park; Hyung Seok Park; Byeong-Woo Park; Joo-Hang Kim; Joohyuk Sohn Journal: PLoS One Date: 2015-03-24 Impact factor: 3.240
Authors: P Bavi; Z Jehan; R Bu; S Prabhakaran; N Al-Sanea; F Al-Dayel; M Al-Assiri; T Al-Halouly; R Sairafi; S Uddin; K S Al-Kuraya Journal: Br J Cancer Date: 2013-10-15 Impact factor: 7.640
Authors: Vijaykumar R Holla; Yasir Y Elamin; Ann Marie Bailey; Amber M Johnson; Beate C Litzenburger; Yekaterina B Khotskaya; Nora S Sanchez; Jia Zeng; Md Abu Shufean; Kenna R Shaw; John Mendelsohn; Gordon B Mills; Funda Meric-Bernstam; George R Simon Journal: Cold Spring Harb Mol Case Stud Date: 2017-01