Applications of array-CGH for lung cancer

Our plain-English summary of Applications of array-CGH for lung cancer, by K.J. Craddock, W.L. Lam, M.S. Tsao (Methods in Molecular Biology, 2013).

The study

• Authors: K.J. Craddock, W.L. Lam, M.S. Tsao
• Journal: Methods in Molecular Biology
• Published: 2013;973:297-324
• Type of article: Review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This chapter summarizes the current knowledge on gene copy number changes found in lung tumors, and their application in the diagnosis, prognostication, and prediction of response to chemotherapy. Examples of the identification of specific "driver" oncogenes within amplified DNA segments are described. A model of how array-CGH could be integrated clinically into the routine workup of lung cancers in clinical laboratory is proposed.

In plain English

This book chapter was a review. The authors summarized published studies that used array comparative genomic hybridization (array-CGH), a method for finding gained or lost DNA segments, in lung cancers. The chapter did not assess asbestos exposure or asbestos-related disease risk. Asbestos is not mentioned; besides smoking, arsenic, nickel and radon are named as environmental carcinogens that have been implicated. A short section covered pleural mesothelioma. In the studies reviewed, losses at 9p involving the CDKN2A and CDKN2B genes were reported in 40–70% of primary mesotheliomas by array-CGH and 70–90% by FISH. None of these changes had been shown to be specific to mesothelioma compared with non-small cell lung cancer, and they were not found in reactive or benign mesothelial lesions. The authors proposed that finding such changes, especially 9p deletion, would give strong evidence for mesothelioma rather than reactive pleural fibrosis. For lung cancer, they noted that prognostic evidence from copy number changes was limited and mostly unvalidated. The authors concluded that copy number information will be an important part of genetic workup for personalized cancer treatment.

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: review (book chapter) of published array-CGH studies of lung tumors
• Who was studied: No new patients were studied. The chapter reviewed published array-CGH studies of lung cancers (non-small cell, small cell, large cell neuroendocrine, carcinoid) and lung cancer cell lines, plus a few studies of pleural mesothelioma.
• Exposure: No asbestos or fiber exposure was assessed. The subject is gene copy number changes measured by array-CGH. The introduction names smoking as the most important cause of lung cancer and says arsenic, nickel and radon have also been implicated as environmental carcinogens. Some reviewed studies reported associations between copy number changes and smoking. Asbestos is not mentioned.
• Main results:
  • In the reviewed mesothelioma studies, the most frequent change was 9p loss involving CDKN2A and CDKN2B. It was reported in 40–70% of primary mesotheliomas by array-CGH and in 70–90% by FISH.
  • None of the recurrent changes in mesothelioma had been shown to be specific to mesothelioma compared with non-small cell lung cancer.
  • Studies cited by the authors found that these abnormalities, especially 9p deletions, were not present in reactive or benign mesothelial lesions such as mesothelial hyperplasia, pleuritis, adenomatoid tumor and benign mesothelial multicystic tumor.
  • Across non-small cell lung cancer, the reviewed studies found frequent gains involving 5p, 8q, 3q and 1q, and frequent losses at 3p, 8p, 9p, 13q and 17p.
  • In one reviewed study of lung adenocarcinoma (Li et al.), copy number gain of EGFR by array-CGH was found in 42/50 (84%) of EGFR-mutated cases and in 7/24 (29%) of wild-type cases.
  • The authors proposed that, when distinguishing reactive pleural fibrosis from mesothelioma, finding any abnormality by array-CGH, particularly 9p deletion, would provide strong evidence for a malignant diagnosis.
• The authors' conclusion: The authors concluded that array-CGH has been a useful tool for understanding genetic imbalances in lung cancer. They also concluded that copy number information will be an important component of the genetic workup needed for personalized cancer treatment.
• Limitations the authors state:
  • The authors stated that little conclusive information is available on using array-CGH changes for prognosis in lung cancer. Many studies did not include patient follow-up.
  • The authors stated that most reported survival associations in lung cancer had not been validated in separate patient cohorts and could be chance findings.
  • The authors stated that small cell lung cancer is hard to study because tumor tissue is scarce, so many studies used cell lines instead.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Chemotherapy.

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