EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues

Maria Paola Martelli, Gabriella Sozzi, Luis Hernandez, Valentina Pettirossi, Alba Navarro, Davide Conte, Patrizia Gasparini, Federica Perrone, Piergiorgio Modena, Ugo Pastorino, Antonino Carbone, Alessandra Fabbri, Angelo Sidoni, Shigeo Nakamura, Marcello Gambacorta, Pedro Luis Fernández, Jose Ramirez, John K C Chan, Walter Franco Grigioni, Elias CampoStefano A. Pileri, Brunangelo Falini

Research output: Contribution to journalArticle

Abstract

A fusion gene, echinoderm microtubule associated protein like 4 - anaplastic lymphoma kinase (EML4-ALK), with transforming activity has recently been identified in a subset of non-small cell lung cancer (NSCLC), but its pathogenetic, diagnostic, and therapeutic roles remain unclear. Both frequency and type of EML4-ALK transcripts were investigated by reverse transcription PCR in 120 frozen NSCLC specimens from Italy and Spain; non-neoplastic lung tissues taken far from the tumor were used as controls. In cases carrying the fusion transcript, we determined EML4-ALK gene and protein levels using fluorescence in situ hybridization, Western blotting, and immunoprecipitation. We also analyzed ALK protein levels in paraffin samples from 662 NSCLC specimens, including the 120 cases investigated in the molecular studies. EML4-ALK transcripts (variants 1 and 3) were detected in 9 of 120 NSCLC samples but were not specific for NSCLC since they were also found in non-cancerous lung tissues taken far from the tumor. Notably, no transcripts were detected in matching tumor samples from these patients. Fluorescence in situ hybridization analysis of cases expressing EML4-ALK transcripts showed that only a minority of cells harbored the EML4-ALK gene. None of these cases was found to express the EML4-ALK protein as examined by immunohistochemistry, Western blotting, and immunoprecipitation. The EML4-ALK transcript cannot be regarded as a specific diagnostic tool for NSCLC. Our results show therefore that the causal role and value of EML4-ALK as a therapeutic target remain to be defined.

Original languageEnglish
Pages (from-to)661-670
Number of pages10
JournalAmerican Journal of Pathology
Volume174
Issue number2
DOIs
Publication statusPublished - Feb 2009

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Non-Small Cell Lung Carcinoma
Lung
Fluorescence In Situ Hybridization
Immunoprecipitation
Western Blotting
anaplastic lymphoma kinase
MAP4
Neoplasms
Proteins
Gene Fusion
Paraffin
Spain
Italy
Reverse Transcription
Immunohistochemistry
Polymerase Chain Reaction
Therapeutics
Genes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Martelli, M. P., Sozzi, G., Hernandez, L., Pettirossi, V., Navarro, A., Conte, D., ... Falini, B. (2009). EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues. American Journal of Pathology, 174(2), 661-670. https://doi.org/10.2353/ajpath.2009.080755

EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues. / Martelli, Maria Paola; Sozzi, Gabriella; Hernandez, Luis; Pettirossi, Valentina; Navarro, Alba; Conte, Davide; Gasparini, Patrizia; Perrone, Federica; Modena, Piergiorgio; Pastorino, Ugo; Carbone, Antonino; Fabbri, Alessandra; Sidoni, Angelo; Nakamura, Shigeo; Gambacorta, Marcello; Fernández, Pedro Luis; Ramirez, Jose; Chan, John K C; Grigioni, Walter Franco; Campo, Elias; Pileri, Stefano A.; Falini, Brunangelo.

In: American Journal of Pathology, Vol. 174, No. 2, 02.2009, p. 661-670.

Research output: Contribution to journalArticle

Martelli, MP, Sozzi, G, Hernandez, L, Pettirossi, V, Navarro, A, Conte, D, Gasparini, P, Perrone, F, Modena, P, Pastorino, U, Carbone, A, Fabbri, A, Sidoni, A, Nakamura, S, Gambacorta, M, Fernández, PL, Ramirez, J, Chan, JKC, Grigioni, WF, Campo, E, Pileri, SA & Falini, B 2009, 'EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues', American Journal of Pathology, vol. 174, no. 2, pp. 661-670. https://doi.org/10.2353/ajpath.2009.080755
Martelli, Maria Paola ; Sozzi, Gabriella ; Hernandez, Luis ; Pettirossi, Valentina ; Navarro, Alba ; Conte, Davide ; Gasparini, Patrizia ; Perrone, Federica ; Modena, Piergiorgio ; Pastorino, Ugo ; Carbone, Antonino ; Fabbri, Alessandra ; Sidoni, Angelo ; Nakamura, Shigeo ; Gambacorta, Marcello ; Fernández, Pedro Luis ; Ramirez, Jose ; Chan, John K C ; Grigioni, Walter Franco ; Campo, Elias ; Pileri, Stefano A. ; Falini, Brunangelo. / EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues. In: American Journal of Pathology. 2009 ; Vol. 174, No. 2. pp. 661-670.
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AU - Navarro, Alba

AU - Conte, Davide

AU - Gasparini, Patrizia

AU - Perrone, Federica

AU - Modena, Piergiorgio

AU - Pastorino, Ugo

AU - Carbone, Antonino

AU - Fabbri, Alessandra

AU - Sidoni, Angelo

AU - Nakamura, Shigeo

AU - Gambacorta, Marcello

AU - Fernández, Pedro Luis

AU - Ramirez, Jose

AU - Chan, John K C

AU - Grigioni, Walter Franco

AU - Campo, Elias

AU - Pileri, Stefano A.

AU - Falini, Brunangelo

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