Journal ArticleDOI
Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma
Isabelle Janoueix-Lerosey,Delphine Lequin,Delphine Lequin,Laurence Brugières,Agnès Ribeiro,Loïc de Pontual,Valérie Combaret,Virginie Raynal,Virginie Raynal,Alain Puisieux,Alain Puisieux,Gudrun Schleiermacher,Gudrun Schleiermacher,Gaëlle Pierron,Dominique Valteau-Couanet,Thierry Frebourg,Jean Michon,Stanislas Lyonnet,Jeanne Amiel,Olivier Delattre,Olivier Delattre +20 more
Reads0
Chats0
TLDR
In this paper, the authors conducted genome-wide comparative genomic hybridization analysis on a large series of neuroblastomas and found that the copy number increase at the locus encoding the anaplastic lymphoma kinase tyrosine kinase receptor was observed recurrently.Abstract:
Neuroblastoma, a tumour derived from the peripheral sympathetic nervous system, is one of the most frequent solid tumours in childhood. It usually occurs sporadically but familial cases are observed, with a subset of cases occurring in association with congenital malformations of the neural crest being linked to germline mutations of the PHOX2B gene. Here we conducted genome-wide comparative genomic hybridization analysis on a large series of neuroblastomas. Copy number increase at the locus encoding the anaplastic lymphoma kinase (ALK) tyrosine kinase receptor was observed recurrently. One particularly informative case presented a high-level gene amplification that was strictly limited to ALK, indicating that this gene may contribute on its own to neuroblastoma development. Through subsequent direct sequencing of cell lines and primary tumour DNAs we identified somatic mutations of the ALK kinase domain that mainly clustered in two hotspots. Germline mutations were observed in two neuroblastoma families, indicating that ALK is a neuroblastoma predisposition gene. Mutated ALK proteins were overexpressed, hyperphosphorylated and showed constitutive kinase activity. The knockdown of ALK expression in ALK-mutated cells, but also in cell lines overexpressing a wild-type ALK, led to a marked decrease of cell proliferation. Altogether, these data identify ALK as a critical player in neuroblastoma development that may hence represent a very attractive therapeutic target in this disease that is still frequently fatal with current treatments.read more
Citations
More filters
Journal ArticleDOI
Recent advances in neuroblastoma.
TL;DR: The author discusses recent advances in the understanding of neuroblastoma, an embryonal cancer of the autonomic nervous system, which has one of the highest rates of spontaneous and complete regression.
Journal ArticleDOI
Mechanisms of Acquired Crizotinib Resistance in ALK-Rearranged Lung Cancers
Ryohei Katayama,Alice T. Shaw,Alice T. Shaw,Tahsin M. Khan,Tahsin M. Khan,Mari Mino-Kenudson,Benjamin Solomon,Balazs Halmos,Nicholas A. Jessop,John C. Wain,Alan Tien Yeo,Cyril H. Benes,Lisa Drew,Jamal Carlos Saeh,Katherine Crosby,Lecia V. Sequist,A. John Iafrate,Jeffrey A. Engelman +17 more
TL;DR: Findings from a series of lung cancer patients with acquired resistance to the ALK TKI crizotinib reinforce the need to tailor therapeutic strategies to the specific underlying drug resistance mechanisms in the tumors to improve clinical outcomes.
Journal ArticleDOI
Advances in understanding cancer genomes through second-generation sequencing
TL;DR: This Review focuses on the methodological considerations for characterizing somatic genome alterations in cancer and the future prospects for these approaches.
Journal ArticleDOI
The genetic landscape of high-risk neuroblastoma
Trevor J. Pugh,Olena Morozova,Edward F. Attiyeh,Edward F. Attiyeh,Shahab Asgharzadeh,Shahab Asgharzadeh,Jun S. Wei,Daniel Auclair,Scott L. Carter,Kristian Cibulskis,Megan Hanna,Megan Hanna,Adam Kiezun,Jaegil Kim,Michael S. Lawrence,Lee Lichenstein,Aaron McKenna,Chandra Sekhar Pedamallu,Chandra Sekhar Pedamallu,Alex H. Ramos,Alex H. Ramos,Erica Shefler,Andrey Sivachenko,Carrie Sougnez,Chip Stewart,Adrian Ally,Inanc Birol,Readman Chiu,Richard Corbett,Martin Hirst,Shaun D. Jackman,Baljit Kamoh,Alireza Hadj Khodabakshi,Martin Krzywinski,Allan Lo,Richard A. Moore,Karen Mungall,Jenny Q. Qian,Angela Tam,Nina Thiessen,Yongjun Zhao,Kristina A. Cole,Kristina A. Cole,Maura Diamond,Maura Diamond,Sharon J. Diskin,Sharon J. Diskin,Yael P. Mosse,Yael P. Mosse,Andrew Wood,Andrew Wood,Lingyun Ji,Lingyun Ji,Richard Sposto,Richard Sposto,Thomas C. Badgett,Wendy B. London,Yvonne Moyer,Yvonne Moyer,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Malcolm A. Smith,Jaime M. Guidry Auvil,Daniela S. Gerhard,Michael D. Hogarty,Michael D. Hogarty,Steven J.M. Jones,Eric S. Lander,Stacey Gabriel,Gad Getz,Robert C. Seeger,Robert C. Seeger,Javed Khan,Marco A. Marra,Matthew Meyerson,Matthew Meyerson,John M. Maris +76 more
TL;DR: The authors reported a low median exonic mutation frequency of 0.60 per Mb (0.48 nonsilent) and notably few recurrently mutated genes in high-risk neuroblastoma.
Journal ArticleDOI
Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis.
Alice T. Shaw,Beow Y. Yeap,Benjamin Solomon,Gregory J. Riely,Justin F. Gainor,Jeffrey A. Engelman,Geoffrey I. Shapiro,Daniel B. Costa,Sai-Hong Ignatius 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 +22 more
TL;DR: In patients with advanced, ALK-positive NSCLC, crizotinib therapy is associated with improved survival compared with that of crizotib-naive controls, and ALK rearrangement is not a favourable prognostic factor in advanced NSClC.
References
More filters
Journal ArticleDOI
Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
Manabu Soda,Young Lim Choi,Munehiro Enomoto,Shuji Takada,Yoshihiro Yamashita,Shunpei Ishikawa,Shin-ichiro Fujiwara,Hideki Watanabe,Kentaro Kurashina,Hisashi Hatanaka,Masashi Bando,Shoji Ohno,Yuichi Ishikawa,Hiroyuki Aburatani,Toshiro Niki,Yasunori Sohara,Yukihiko Sugiyama,Hiroyuki Mano +17 more
TL;DR: It is shown that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC) cells.
Journal ArticleDOI
Oncogenic kinase signalling
Peter Blume-Jensen,Tony Hunter +1 more
TL;DR: How oncogenic conversion of protein kinases results from perturbation of the normal autoinhibitory constraints on kinase activity is emphasized and an update is provided on the role of deregulated PI(3)K/Akt and mammalian target of rapamycin/p70S6K signalling in human malignancies.
Journal ArticleDOI
Fusion of a Kinase Gene, ALK, to a Nucleolar Protein Gene, NPM, in Non-Hodgkin's Lymphoma
Stephan W. Morris,Mark N. Kirstein,Marcus B. Valentine,KG Dittmer,KG Dittmer,David N. Shapiro,David N. Shapiro,D. L. Saltman,AT Look,AT Look +9 more
TL;DR: In the predicted hybrid protein, the amino terminus of nucleophosmin (NPM) is linked to the catalytic domain of anaplastic lymphoma kinase (ALK), and unscheduled expression of the truncated ALK may contribute to malignant transformation in these lymphomas.
Journal ArticleDOI
Global Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer
Klarisa Rikova,Ailan Guo,Qingfu Zeng,Anthony Possemato,Jian Yu,Herbert Haack,Julie Nardone,Kimberly Lee,Cynthia Reeves,Yu Li,Yerong Hu,Zhi-Ping Tan,Matthew P. Stokes,Laura Sullivan,Jeffrey Mitchell,Randy Wetzel,Joan MacNeill,Jian Min Ren,Jin Yuan,Corey E. Bakalarski,Judit Villén,Jon M. Kornhauser,Bradley L. Smith,Daiqiang Li,Xinmin Zhou,Steven P. Gygi,Ting-Lei Gu,Roberto D. Polakiewicz,John Rush,Michael J. Comb +29 more
TL;DR: By focusing on activated cell circuitry, the approach outlined here provides insight into cancer biology not available at the chromosomal and transcriptional levels and can be applied broadly across all human cancers.
Journal ArticleDOI
Neuroblastoma: biological insights into a clinical enigma.
TL;DR: Recent advances in understanding the biology and genetics of neuroblastomas have allowed classification into low-, intermediate- and high-risk groups, which allows the most appropriate intensity of therapy to be selected — from observation alone to aggressive, multimodality therapy.
Related Papers (5)
Identification of ALK as a major familial neuroblastoma predisposition gene
Yael P. Mosse,Marci Laudenslager,Luca Longo,Kristina A. Cole,Andrew C. Wood,Edward F. Attiyeh,Michael J. Laquaglia,Rachel Sennett,Jill E. Lynch,Patrizia Perri,Genevieve Laureys,Frank Speleman,Cecilia Kim,Cuiping Hou,Cuiping Hou,Hakon Hakonarson,Hakon Hakonarson,Ali Torkamani,Nicholas J. Schork,Garrett M. Brodeur,Gian Paolo Tonini,Eric F. Rappaport,Marcella Devoto,Marcella Devoto,John M. Maris +24 more
Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer
Eunice L. Kwak,Yung-Jue Bang,D. Ross Camidge,Alice T. Shaw,Benjamin Solomon,Robert G. Maki,Sai-Hong Ignatius Ou,Bruce J. Dezube,Pasi A. Jänne,Daniel B. Costa,Marileila Varella-Garcia,Woo-Ho Kim,Thomas J. Lynch,Panos Fidias,Hannah Stubbs,Jeffrey A. Engelman,Lecia V. Sequist,Weiwei Tan,Leena Gandhi,Mari Mino-Kenudson,Greg C. Wei,S. Martin Shreeve,Mark J. Ratain,Jeffrey Settleman,James G. Christensen,Daniel A. Haber,Keith D. Wilner,Ravi Salgia,Geoffrey I. Shapiro,Jeffrey W. Clark,A. John Iafrate +30 more