Oncogenic mutation profiling in new lung cancer and mesothelioma cell lines

Our plain-English summary of Oncogenic mutation profiling in new lung cancer and mesothelioma cell lines, by D.C. Lam, S.Y. Luo, W. Deng, et al (OncoTargets and Therapy, 2015).

The study

• Authors: D.C. Lam, S.Y. Luo, W. Deng, J.S.H. Kwan, J. Rodriguez-Canales, A.L. Cheung, G.H. Cheng, C.H. Lin, I.I. Wistuba, P.C. Sham, T.S. Wan, S.W. Tsao
• Journal: OncoTargets and Therapy
• Published: 2015;8:195-209
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Thoracic tumor, especially lung cancer, ranks as the top cancer mortality in most parts of the world. Lung adenocarcinoma is the predominant subtype and there is increasing knowledge on therapeutic molecular targets, namely EGFR, ALK, KRAS, and ROS1, among lung cancers. Lung cancer cell lines established with known clinical characteristics and molecular profiling of oncogenic targets like ALK or KRAS could be useful tools for understanding the biology of known molecular targets as well as for drug testing and screening.

Materials And Methods: Five new cancer cell lines were established from pleural fluid or biopsy tissues obtained from Chinese patients with primary lung adenocarcinomas or malignant pleural mesothelioma. They were characterized by immunohistochemistry, growth kinetics, tests for tumorigenicity, EGFR and KRAS gene mutations, ALK gene rearrangement and OncoSeq mutation profiling.

Results: These newly established lung adenocarcinoma and mesothelioma cell lines were maintained for over 100 passages and demonstrated morphological and immunohistochemical features as well as growth kinetics of tumor cell lines. One of these new cell lines bears EML4-ALK rearrangement variant 2, two lung cancer cell lines bear different KRAS mutations at codon 12, and known single nucleotide polymorphism variants were identified in these cell lines.

Discussion: Four new lung adenocarcinoma and one mesothelioma cell lines were established from patients with different clinical characteristics and oncogenic mutation profiles. These characterized cell lines and their mutation profiles will provide resources for exploration of lung cancer and mesothelioma biology with regard to the presence of known oncogenic mutations.

In plain English

This laboratory study set up five new cancer cell lines (cancer cells that keep growing in the lab) from Chinese patients with stage IV disease in Hong Kong. Four came from lung adenocarcinoma. One, called PME1, came from malignant pleural mesothelioma in a 73-year-old man who had retired from incinerator service with exposure to asbestos. The article gave no fiber type or amount of exposure. All five lines were kept growing for over 100 passages. The results section reported that PME1 stained positive for vimentin and negative for mucin, WT1 and calretinin. The four lung lines formed tumors when injected into nude mice, but PME1 did not. No line had EGFR mutations in exons 18 to 21, the region tested. One lung line carried an EML4-ALK rearrangement and two carried KRAS codon 12 mutations; PME1 had no KRAS mutation at the codons tested. All five lines showed losses or partial deletions of chromosome 13, and a WRN gene variant was reported in PME1. The authors concluded that the lines could add to existing collections, mostly from non-Asian patients, for laboratory and drug-sensitivity studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study establishing and characterizing new human cancer cell lines, including tumor-formation tests in nude mice
• Who was studied: Five cell lines from Chinese patients at the University of Hong Kong/Queen Mary Hospital, all stage IV: four lung adenocarcinoma lines (FA34, FA44, FA49, FA98) and one malignant pleural mesothelioma line (PME1) from a 73-year-old man. No collection dates were given, except that the FA34 patient died in 2008.
• Exposure: The study did not examine exposure. The only asbestos information concerns the mesothelioma patient, who had retired from incinerator service with exposure to asbestos. No fiber type, duration or dose was reported.
• Main results:
  • All five cell lines were maintained for over 100 passages
  • In the results section, the mesothelioma line PME1 stained positive for vimentin and negative for mucin, WT1 and calretinin, which the authors said suggested mesothelial origin
  • Doubling time was about 22 hours for FA44, FA49, FA98 and PME1, and around 34 hours for FA34
  • All four adenocarcinoma lines formed xenograft tumors in nude mice; the mesothelioma line PME1 produced no xenograft
  • None of the five lines had EGFR mutations at exons 18 to 21, the region tested by direct sequencing; the broader gene-panel screen separately reported an EGFR exon 13 variant predicted to be tolerated
  • Lung lines FA44 and FA49 had KRAS codon 12 mutations (G215T and G219A); FA34, FA98 and PME1 had no KRAS mutation at codons 12, 13 or 61
  • Lung line FA34 carried an EML4-ALK rearrangement, variant 2
  • Losses or partial deletions of chromosome 13 were seen in all five lines
  • Gene-panel sequencing of 142 cancer genes found 42 variants in 27 genes across the lines; a WRN gene variant was reported in PME1
• The authors' conclusion: The authors concluded that they had established four new lung adenocarcinoma lines and one new malignant mesothelioma line from Chinese patients, with differing characteristics and mutation profiles. They said these lines could add to available cell lines, most of which come from non-Asian patients, for functional studies and drug sensitivity testing.
• Limitations the authors state:
  • The sequencing panel was limited to a set of known oncogenic genes and served only as a screening tool

Topics

Medical terms in this study, explained in our Lexicon: Lung Cancer, Mesothelioma, Lung Adenocarcinoma, EGFR, ROS1, Molecular Profiling, Biopsy, Pleural Mesothelioma.

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