Cargando…

Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer

Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) is routinely evaluated by fluorescent in-situ hybridization (FISH) testing on biopsy tissues. Testing can be challenging however, when suitable tissue samples are unavailable. We examined the relevance of circu...

Descripción completa

Detalles Bibliográficos
Autores principales: Tan, Chye Ling, Lim, Tse Hui, Lim, Tony KH, Tan, Daniel Shao-Weng, Chua, Yong Wei, Ang, Mei Kim, Pang, Brendan, Lim, Chwee Teck, Takano, Angela, Lim, Alvin Soon-Tiong, Leong, Man Chun, Lim, Wan-Teck
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029624/
https://www.ncbi.nlm.nih.gov/pubmed/26993609
http://dx.doi.org/10.18632/oncotarget.8136
_version_ 1782454543541338112
author Tan, Chye Ling
Lim, Tse Hui
Lim, Tony KH
Tan, Daniel Shao-Weng
Chua, Yong Wei
Ang, Mei Kim
Pang, Brendan
Lim, Chwee Teck
Takano, Angela
Lim, Alvin Soon-Tiong
Leong, Man Chun
Lim, Wan-Teck
author_facet Tan, Chye Ling
Lim, Tse Hui
Lim, Tony KH
Tan, Daniel Shao-Weng
Chua, Yong Wei
Ang, Mei Kim
Pang, Brendan
Lim, Chwee Teck
Takano, Angela
Lim, Alvin Soon-Tiong
Leong, Man Chun
Lim, Wan-Teck
author_sort Tan, Chye Ling
collection PubMed
description Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) is routinely evaluated by fluorescent in-situ hybridization (FISH) testing on biopsy tissues. Testing can be challenging however, when suitable tissue samples are unavailable. We examined the relevance of circulating tumor cells (CTC) as a surrogate for biopsy-based FISH testing. We assessed paired tumor and CTC samples from patients with ALK rearranged lung cancer (n = 14), ALK-negative lung cancer (n = 12), and healthy controls (n = 5) to derive discriminant CTC counts, and to compare ALK rearrangement patterns. Blood samples were enriched for CTCs to be used for ALK FISH testing. ALK-positive CTCs counts were higher in ALK-positive NSCLC patients (3–15 cells/1.88 mL of blood) compared with ALK-negative NSCLC patients and healthy donors (0–2 cells/1.88 mL of blood). The latter range was validated as the ‘false positive’ cutoff for ALK FISH testing of CTCs. ALK FISH signal patterns observed on tumor biopsies were recapitulated in CTCs in all cases. Sequential CTC counts in an index case of lung cancer with no evaluable tumor tissue treated with crizotinib showed six, three and eleven ALK-positive CTCs per 1.88 mL blood at baseline, partial response and post-progression time points, respectively. Furthermore, ALK FISH rearrangement suggestive of gene copy number increase was observed in CTCs following progression. Recapitulation of ALK rearrangement patterns in the tumor on CTCs, suggested that CTCs might be used to complement tissue-based ALK testing in NSCLC to guide ALK-targeted therapy when suitable tissue biopsy samples are unavailable for testing.
format Online
Article
Text
id pubmed-5029624
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-50296242016-09-29 Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer Tan, Chye Ling Lim, Tse Hui Lim, Tony KH Tan, Daniel Shao-Weng Chua, Yong Wei Ang, Mei Kim Pang, Brendan Lim, Chwee Teck Takano, Angela Lim, Alvin Soon-Tiong Leong, Man Chun Lim, Wan-Teck Oncotarget Research Paper Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) is routinely evaluated by fluorescent in-situ hybridization (FISH) testing on biopsy tissues. Testing can be challenging however, when suitable tissue samples are unavailable. We examined the relevance of circulating tumor cells (CTC) as a surrogate for biopsy-based FISH testing. We assessed paired tumor and CTC samples from patients with ALK rearranged lung cancer (n = 14), ALK-negative lung cancer (n = 12), and healthy controls (n = 5) to derive discriminant CTC counts, and to compare ALK rearrangement patterns. Blood samples were enriched for CTCs to be used for ALK FISH testing. ALK-positive CTCs counts were higher in ALK-positive NSCLC patients (3–15 cells/1.88 mL of blood) compared with ALK-negative NSCLC patients and healthy donors (0–2 cells/1.88 mL of blood). The latter range was validated as the ‘false positive’ cutoff for ALK FISH testing of CTCs. ALK FISH signal patterns observed on tumor biopsies were recapitulated in CTCs in all cases. Sequential CTC counts in an index case of lung cancer with no evaluable tumor tissue treated with crizotinib showed six, three and eleven ALK-positive CTCs per 1.88 mL blood at baseline, partial response and post-progression time points, respectively. Furthermore, ALK FISH rearrangement suggestive of gene copy number increase was observed in CTCs following progression. Recapitulation of ALK rearrangement patterns in the tumor on CTCs, suggested that CTCs might be used to complement tissue-based ALK testing in NSCLC to guide ALK-targeted therapy when suitable tissue biopsy samples are unavailable for testing. Impact Journals LLC 2016-03-16 /pmc/articles/PMC5029624/ /pubmed/26993609 http://dx.doi.org/10.18632/oncotarget.8136 Text en Copyright: © 2016 Tan et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Tan, Chye Ling
Lim, Tse Hui
Lim, Tony KH
Tan, Daniel Shao-Weng
Chua, Yong Wei
Ang, Mei Kim
Pang, Brendan
Lim, Chwee Teck
Takano, Angela
Lim, Alvin Soon-Tiong
Leong, Man Chun
Lim, Wan-Teck
Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer
title Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer
title_full Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer
title_fullStr Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer
title_full_unstemmed Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer
title_short Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer
title_sort concordance of anaplastic lymphoma kinase (alk) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029624/
https://www.ncbi.nlm.nih.gov/pubmed/26993609
http://dx.doi.org/10.18632/oncotarget.8136
work_keys_str_mv AT tanchyeling concordanceofanaplasticlymphomakinasealkgenerearrangementsbetweencirculatingtumorcellsandtumorinnonsmallcelllungcancer
AT limtsehui concordanceofanaplasticlymphomakinasealkgenerearrangementsbetweencirculatingtumorcellsandtumorinnonsmallcelllungcancer
AT limtonykh concordanceofanaplasticlymphomakinasealkgenerearrangementsbetweencirculatingtumorcellsandtumorinnonsmallcelllungcancer
AT tandanielshaoweng concordanceofanaplasticlymphomakinasealkgenerearrangementsbetweencirculatingtumorcellsandtumorinnonsmallcelllungcancer
AT chuayongwei concordanceofanaplasticlymphomakinasealkgenerearrangementsbetweencirculatingtumorcellsandtumorinnonsmallcelllungcancer
AT angmeikim concordanceofanaplasticlymphomakinasealkgenerearrangementsbetweencirculatingtumorcellsandtumorinnonsmallcelllungcancer
AT pangbrendan concordanceofanaplasticlymphomakinasealkgenerearrangementsbetweencirculatingtumorcellsandtumorinnonsmallcelllungcancer
AT limchweeteck concordanceofanaplasticlymphomakinasealkgenerearrangementsbetweencirculatingtumorcellsandtumorinnonsmallcelllungcancer
AT takanoangela concordanceofanaplasticlymphomakinasealkgenerearrangementsbetweencirculatingtumorcellsandtumorinnonsmallcelllungcancer
AT limalvinsoontiong concordanceofanaplasticlymphomakinasealkgenerearrangementsbetweencirculatingtumorcellsandtumorinnonsmallcelllungcancer
AT leongmanchun concordanceofanaplasticlymphomakinasealkgenerearrangementsbetweencirculatingtumorcellsandtumorinnonsmallcelllungcancer
AT limwanteck concordanceofanaplasticlymphomakinasealkgenerearrangementsbetweencirculatingtumorcellsandtumorinnonsmallcelllungcancer