BACKGROUND: Anaplastic lymphoma kinase (ALK) fusion oncogenes are present in multiple cancer types. The inversion of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) genes on chromosome 2 is present in a subset of patients with non-small-cell lung cancer (NSCLC). ALK-rearranged lung cancers demonstrate a significantly higher incidence of signet ring cell histology than do ALK-negative tumors. Based on the histologic similarities of ALK-rearranged NSCLC and signet ring cell carcinomas (SRCCs) of the gastrointestinal tract, we hypothesized that SRCC of the upper gastrointestinal (GI) tract may also harbor ALK translocations. METHODS: Thirty-five formalin-fixed, paraffin-embedded (FFPE) diagnostic tissue specimens of SRCC or poorly differentiated adenocarcinoma with greater than 10% signet ring cell features originating from the upper GI tract were obtained and confirmed by a board-certified, GI pathologist. SRCC specimens were analyzed by fluorescence in situ hybridization (FISH) analysis, with an ALK (2p23) break-apart probe. RESULTS: The FISH analysis revealed no evidence of ALK translocation. All 35 (100%) SRCC specimens showed intact ALK FISH signals. CONCLUSIONS: These data indicate that, despite histologic similarities between SRCC of the upper GI tract and ALK-positive NSCLC, ALK translocations are unlikely to be a significant contributor to the molecular etiology of SRCC. Further genomic investigations are ongoing.
BACKGROUND:Anaplastic lymphoma kinase (ALK) fusion oncogenes are present in multiple cancer types. The inversion of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) genes on chromosome 2 is present in a subset of patients with non-small-cell lung cancer (NSCLC). ALK-rearranged lung cancers demonstrate a significantly higher incidence of signet ring cell histology than do ALK-negative tumors. Based on the histologic similarities of ALK-rearranged NSCLC and signet ring cell carcinomas (SRCCs) of the gastrointestinal tract, we hypothesized that SRCC of the upper gastrointestinal (GI) tract may also harbor ALK translocations. METHODS: Thirty-five formalin-fixed, paraffin-embedded (FFPE) diagnostic tissue specimens of SRCC or poorly differentiated adenocarcinoma with greater than 10% signet ring cell features originating from the upper GI tract were obtained and confirmed by a board-certified, GI pathologist. SRCC specimens were analyzed by fluorescence in situ hybridization (FISH) analysis, with an ALK (2p23) break-apart probe. RESULTS: The FISH analysis revealed no evidence of ALK translocation. All 35 (100%) SRCC specimens showed intact ALK FISH signals. CONCLUSIONS: These data indicate that, despite histologic similarities between SRCC of the upper GI tract and ALK-positive NSCLC, ALK translocations are unlikely to be a significant contributor to the molecular etiology of SRCC. Further genomic investigations are ongoing.
Authors: Alice T Shaw; Beow Y Yeap; Benjamin J Solomon; Gregory J Riely; Justin Gainor; Jeffrey A Engelman; Geoffrey I Shapiro; Daniel B Costa; Sai-Hong I Ou; Mohit Butaney; Ravi Salgia; Robert G Maki; Marileila Varella-Garcia; Robert C Doebele; Yung-Jue Bang; Kimary Kulig; Paulina Selaru; Yiyun Tang; Keith D Wilner; Eunice L Kwak; Jeffrey W Clark; A John Iafrate; D Ross Camidge Journal: Lancet Oncol Date: 2011-09-18 Impact factor: 41.316
Authors: D G Huntsman; F Carneiro; F R Lewis; P M MacLeod; A Hayashi; K G Monaghan; R Maung; R Seruca; C E Jackson; C Caldas Journal: N Engl J Med Date: 2001-06-21 Impact factor: 91.245
Authors: Gianpaolo Suriano; Sandie Yew; Paulo Ferreira; Janine Senz; Pardeep Kaurah; James M Ford; Teri A Longacre; Jeffrey A Norton; Nicki Chun; Sean Young; Maria J Oliveira; Barbara Macgillivray; Arundhati Rao; Dawn Sears; Charles E Jackson; Jeff Boyd; Cindy Yee; Carolyn Deters; G Shashidhar Pai; Lyn S Hammond; Bobbi J McGivern; Diane Medgyesy; Denise Sartz; Banu Arun; Brant K Oelschlager; Mellisa P Upton; Whitney Neufeld-Kaiser; Orlando E Silva; Talia R Donenberg; David A Kooby; Shobha Sharma; Björn-Anders Jonsson; Henrik Gronberg; Steve Gallinger; Raquel Seruca; Henry Lynch; David G Huntsman Journal: Clin Cancer Res Date: 2005-08-01 Impact factor: 12.531
Authors: S W Morris; M N Kirstein; M B Valentine; K G Dittmer; D N Shapiro; D L Saltman; A T Look Journal: Science Date: 1994-03-04 Impact factor: 47.728