Malignant cells from pleural fluids in malignant mesothelioma patients reveal novel mutations

Sophie Ann Sneddon, Ian Malcolm Dick, Yun Chor Lee, Arthur William Musk, Richard James Allcock, N Waddell, A.-M. Patch, J.V. Pearson, Robert Andrew Holt, Bruce William Robinson, Jenette Creaney

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objectives
Malignant mesothelioma (MM) is an asbestos related tumour affecting cells of serosal cavities. More than 70% of MM patients develop pleural effusions which contain tumour cells, representing a readily accessible source of malignant cells for genetic analysis. Although common somatic mutations and losses have been identified in solid MM tumours, the characterization of tumour cells within pleural effusions could provide novel insights but is little studied.

Materials and methods
DNA and RNA were extracted from cells from short term cultures of 27 human MM pleural effusion samples. Whole exome and transcriptome sequencing was performed using the Ion Torrent platform. Somatic mutations were identified using VarScan2 and SomaticSniper. Copy number alterations were identified using ExomeCNV in R. Significant copy number alterations were identified across all samples using GISTIC2.0. The association between tumour intrinsic properties and survival was analyzed using the Cox proportional hazards regression model.

Results
We identified BAP1, CDKN2A and NF2 alterations in the cells from MM pleural effusions at a higher frequency than what is typically seen in MM tumours from surgical series. The median mutation rate was 1.09 mutations/Mb. TRAF7 and LATS2 alterations were also identified at a high frequency (66% and 59% respectively). Novel regions of interest were identified, including alterations in FGFR3, and the regions 19p13.3, 8p23.1 and 1p36.32.

Conclusion
Short term cultures of tumour cells from MM pleural effusions offer an accessible alternative to surgical tumour biopsies in the study of MM genomics and reveal novel mutations of interest. Pleural effusion tumour cells provide an opportunity for the monitoring of tumour dynamics, treatment response and the clonal evolution of MM tumours.
Original languageEnglish
Pages (from-to)64-70
JournalLung Cancer
Volume119
DOIs
Publication statusPublished - May 2018

Fingerprint

Mesothelioma
Mutation
Pleural Effusion
Neoplasms
Malignant Mesothelioma
Clonal Evolution
Exome
Asbestos
Mutation Rate
Genomics
Transcriptome
Proportional Hazards Models
Cell Culture Techniques
RNA
Ions
Biopsy
Survival

Cite this

@article{c5251f0907f54fb1833298bf98f4fc0d,
title = "Malignant cells from pleural fluids in malignant mesothelioma patients reveal novel mutations",
abstract = "ObjectivesMalignant mesothelioma (MM) is an asbestos related tumour affecting cells of serosal cavities. More than 70{\%} of MM patients develop pleural effusions which contain tumour cells, representing a readily accessible source of malignant cells for genetic analysis. Although common somatic mutations and losses have been identified in solid MM tumours, the characterization of tumour cells within pleural effusions could provide novel insights but is little studied.Materials and methodsDNA and RNA were extracted from cells from short term cultures of 27 human MM pleural effusion samples. Whole exome and transcriptome sequencing was performed using the Ion Torrent platform. Somatic mutations were identified using VarScan2 and SomaticSniper. Copy number alterations were identified using ExomeCNV in R. Significant copy number alterations were identified across all samples using GISTIC2.0. The association between tumour intrinsic properties and survival was analyzed using the Cox proportional hazards regression model.ResultsWe identified BAP1, CDKN2A and NF2 alterations in the cells from MM pleural effusions at a higher frequency than what is typically seen in MM tumours from surgical series. The median mutation rate was 1.09 mutations/Mb. TRAF7 and LATS2 alterations were also identified at a high frequency (66{\%} and 59{\%} respectively). Novel regions of interest were identified, including alterations in FGFR3, and the regions 19p13.3, 8p23.1 and 1p36.32.ConclusionShort term cultures of tumour cells from MM pleural effusions offer an accessible alternative to surgical tumour biopsies in the study of MM genomics and reveal novel mutations of interest. Pleural effusion tumour cells provide an opportunity for the monitoring of tumour dynamics, treatment response and the clonal evolution of MM tumours.",
author = "Sneddon, {Sophie Ann} and Dick, {Ian Malcolm} and Lee, {Yun Chor} and Musk, {Arthur William} and Allcock, {Richard James} and N Waddell and A.-M. Patch and J.V. Pearson and Holt, {Robert Andrew} and Robinson, {Bruce William} and Jenette Creaney",
year = "2018",
month = "5",
doi = "10.1016/j.lungcan.2018.03.009",
language = "English",
volume = "119",
pages = "64--70",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier",

}

Malignant cells from pleural fluids in malignant mesothelioma patients reveal novel mutations. / Sneddon, Sophie Ann; Dick, Ian Malcolm; Lee, Yun Chor; Musk, Arthur William; Allcock, Richard James; Waddell, N; Patch, A.-M.; Pearson, J.V.; Holt, Robert Andrew; Robinson, Bruce William; Creaney, Jenette.

In: Lung Cancer, Vol. 119, 05.2018, p. 64-70.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Malignant cells from pleural fluids in malignant mesothelioma patients reveal novel mutations

AU - Sneddon, Sophie Ann

AU - Dick, Ian Malcolm

AU - Lee, Yun Chor

AU - Musk, Arthur William

AU - Allcock, Richard James

AU - Waddell, N

AU - Patch, A.-M.

AU - Pearson, J.V.

AU - Holt, Robert Andrew

AU - Robinson, Bruce William

AU - Creaney, Jenette

PY - 2018/5

Y1 - 2018/5

N2 - ObjectivesMalignant mesothelioma (MM) is an asbestos related tumour affecting cells of serosal cavities. More than 70% of MM patients develop pleural effusions which contain tumour cells, representing a readily accessible source of malignant cells for genetic analysis. Although common somatic mutations and losses have been identified in solid MM tumours, the characterization of tumour cells within pleural effusions could provide novel insights but is little studied.Materials and methodsDNA and RNA were extracted from cells from short term cultures of 27 human MM pleural effusion samples. Whole exome and transcriptome sequencing was performed using the Ion Torrent platform. Somatic mutations were identified using VarScan2 and SomaticSniper. Copy number alterations were identified using ExomeCNV in R. Significant copy number alterations were identified across all samples using GISTIC2.0. The association between tumour intrinsic properties and survival was analyzed using the Cox proportional hazards regression model.ResultsWe identified BAP1, CDKN2A and NF2 alterations in the cells from MM pleural effusions at a higher frequency than what is typically seen in MM tumours from surgical series. The median mutation rate was 1.09 mutations/Mb. TRAF7 and LATS2 alterations were also identified at a high frequency (66% and 59% respectively). Novel regions of interest were identified, including alterations in FGFR3, and the regions 19p13.3, 8p23.1 and 1p36.32.ConclusionShort term cultures of tumour cells from MM pleural effusions offer an accessible alternative to surgical tumour biopsies in the study of MM genomics and reveal novel mutations of interest. Pleural effusion tumour cells provide an opportunity for the monitoring of tumour dynamics, treatment response and the clonal evolution of MM tumours.

AB - ObjectivesMalignant mesothelioma (MM) is an asbestos related tumour affecting cells of serosal cavities. More than 70% of MM patients develop pleural effusions which contain tumour cells, representing a readily accessible source of malignant cells for genetic analysis. Although common somatic mutations and losses have been identified in solid MM tumours, the characterization of tumour cells within pleural effusions could provide novel insights but is little studied.Materials and methodsDNA and RNA were extracted from cells from short term cultures of 27 human MM pleural effusion samples. Whole exome and transcriptome sequencing was performed using the Ion Torrent platform. Somatic mutations were identified using VarScan2 and SomaticSniper. Copy number alterations were identified using ExomeCNV in R. Significant copy number alterations were identified across all samples using GISTIC2.0. The association between tumour intrinsic properties and survival was analyzed using the Cox proportional hazards regression model.ResultsWe identified BAP1, CDKN2A and NF2 alterations in the cells from MM pleural effusions at a higher frequency than what is typically seen in MM tumours from surgical series. The median mutation rate was 1.09 mutations/Mb. TRAF7 and LATS2 alterations were also identified at a high frequency (66% and 59% respectively). Novel regions of interest were identified, including alterations in FGFR3, and the regions 19p13.3, 8p23.1 and 1p36.32.ConclusionShort term cultures of tumour cells from MM pleural effusions offer an accessible alternative to surgical tumour biopsies in the study of MM genomics and reveal novel mutations of interest. Pleural effusion tumour cells provide an opportunity for the monitoring of tumour dynamics, treatment response and the clonal evolution of MM tumours.

U2 - 10.1016/j.lungcan.2018.03.009

DO - 10.1016/j.lungcan.2018.03.009

M3 - Article

VL - 119

SP - 64

EP - 70

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

ER -