Expression and Gene Amplification of Actinin-4 in Invasive Ductal Carcinoma of the Pancreas
Satoru Kikuchi,Kazufumi Honda,Hitoshi Tsuda,Nobuyoshi Hiraoka,Issei Imoto,Tomoo Kosuge,Tomoko Umaki,Kaoru Onozato,Miki Shitashige,Umio Yamaguchi,Masaya Ono,Akihiko Tsuchida,Tatsuya Aoki,Johji Inazawa,Setsuo Hirohashi,Tesshi Yamada +15 more
TLDR
Recurrent amplification of chromosome 19q13.1-2 has been reported in pancreatic cancer, but the exact target gene has not been identified and actinin-4 contributes to the invasive growth of pancreatic ductal carcinoma, and ACTN4 is one of the candidate oncogenes in this chromosome locus.Abstract:
Purpose: An invasive growth pattern is one of the hallmarks of pancreatic ductal carcinoma. Actinin-4 is an actin-binding protein associated with enhanced cell motility, invasive growth, and lymph node metastasis. Actinin-4 might play an important role in the development and progression of pancreatic cancer. Experimental Design: The expression of actinin-4 was examined immunohistochemically in 173 cases of invasive pancreatic ductal carcinoma. The copy number of the actinin-4 ( ACTN4 ) gene was calculated by fluorescence in situ hybridization. The expression of actinin-4 was stably knocked down by short hairpin RNA, and tumorigenicity was evaluated by orthotopic implantation into mice with severe combined immunodeficiency. Results: The expression level of actinin-4 was increased in 109 (63.0%) of 173 cases of pancreatic cancer. Kaplan-Meier survival curves revealed that patients with increased expression of actinin-4 had a significantly poorer outcome ( P = 0.00001, log-rank test). Multivariate analysis by the Cox proportional hazard model showed that high expression of actinin-4 was the most significant independent negative predictor of survival (hazard ratio, 2.33; P = 0.000009). Amplification (defined as more than four copies per interphase nucleus) of the ACTN4 gene was detected in 11 (37.9%) of 29 cases showing increased expression of actinin-4. Knockdown of actinin-4 expression inhibited the destructive growth of cancer cells in the pancreatic parenchyma. Conclusion: Recurrent amplification of chromosome 19q13.1-2 has been reported in pancreatic cancer, but the exact target gene has not been identified. Actinin-4 contributes to the invasive growth of pancreatic ductal carcinoma, and ACTN4 is one of the candidate oncogenes in this chromosome locus.read more
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ORIGINAL ARTICLE New insights to the MLL recombinome of acute leukemias
Cathy Meyer,Eric Kowarz,Julia Hofmann,Aline Renneville,Jan Zuna,Jan Trka,R Ben Abdelali,Elisabeth Macintyre,E De Braekeleer,L Trakhtenbrot,L Lo Nigro,G Tsaur,L Fechina,Tomasz Szczepański,Sabine Strehl,D Ilencikova,M Molkentin,Thomas Burmeister,Theodor Dingermann,Thomas Klingebiel,Rolf Marschalek,Erasmus Mc,Michael Smith +22 more
TL;DR: The genetic network of reciprocal MLL gene fusions deriving from complex rearrangements is described for the first time, and the distribution of MLL breakpoints for clinical subtypes and fused translocation partner genes (TPGs) will be presented, including novel MLL fusion genes.
Journal ArticleDOI
New insights to the MLL recombinome of acute leukemias
Christian Meyer,Eric Kowarz,Julia Hofmann,Aline Renneville,Jan Zuna,Jan Trka,R. Ben Abdelali,Elizabeth Macintyre,E De Braekeleer,E De Braekeleer,M. De Braekeleer,M. De Braekeleer,Eric Delabesse,M. P. de Oliveira,Hélène Cavé,Emmanuelle Clappier,J J M van Dongen,Brian V. Balgobind,M M van den Heuvel-Eibrink,H B Beverloo,Renate Panzer-Grümayer,Andrea Teigler-Schlegel,Jochen Harbott,Eigil Kjeldsen,Susanne Schnittger,Ulrike Koehl,Bernd Gruhn,Olaf Heidenreich,Li Chong Chan,Sze-Fai Yip,Martin Krzywinski,C Eckert,Anja Möricke,Martin Schrappe,Cristina N. Alonso,Beat W. Schäfer,Jürgen Krauter,Dean A. Lee,U zur Stadt,G te Kronnie,Rosemary Sutton,Shai Izraeli,L. Trakhtenbrot,L. Trakhtenbrot,L Lo Nigro,Grigory Tsaur,Larisa Fechina,Tomasz Szczepański,Sabine Strehl,D. Ilencikova,Mara Molkentin,Thomas Burmeister,Theodor Dingermann,T. Klingebiel,Rolf Marschalek +54 more
TL;DR: In this paper, the distribution of MLL breakpoints for clinical subtypes (acute lymphoblastic leukemia, acute myeloid leukemia, pediatric and adult) and fused translocation partner genes (TPGs) were presented, including novel MLL fusion genes.
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Actin-bundling proteins in cancer progression at a glance
TL;DR: Cells use their cytoskeletons to move, polarise, divide and maintain organisation within multicellular tissues, which are constantly remodelled by more than 100 different actin-binding proteins.
Journal ArticleDOI
Tissue Biomarkers for Prognosis in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis
TL;DR: A systematic review and meta-analysis of the published literature for immunohistochemical biomarkers of PDAC outcome found that there was incomplete adherence to the REMARK guidelines with inadequate methodology reporting as well as failure to perform multivariate analysis.
Journal ArticleDOI
The actinin family of actin cross-linking proteins – a genetic perspective
Anita C.H. Murphy,Paul Young +1 more
TL;DR: The human genetics of theACTN gene family is discussed, as well as ACTN gene knockout studies in several model organisms, which provide insights into the evolution and cellular functions of actinins.
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