Genetic Changes in Squamous Cell Lung Cancer A Review

Department of Hematology Oncology, Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer (Impact Factor: 5.8). 05/2012; 7(5):924-33. DOI: 10.1097/JTO.0b013e31824cc334
Source: PubMed

ABSTRACT Identifying specific somatic mutations that drive tumor growth has transformed the treatment of lung cancer. For example, cancers with sensitizing epidermal growth factor receptor mutations and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase translocations can have remarkable responses to epidermal growth factor receptor and ALK inhibitors respectively, leading to significant clinical benefit. However, effective molecularly targeted therapies have disproportionately impacted adenocarcinomas compared to squamous cell carcinomas, and never or light smokers compared to heavy smokers. Further progress in non-small-cell lung cancer will require the identification and effective targeting of molecular alterations in all subtypes of lung cancer. Here, we review the current knowledge about the molecular alterations found in squamous cell carcinoma of the lung. First, we will discuss the ongoing efforts to comprehensively assess the squamous cell carcinoma genome. We will then discuss the evidence supporting the role of specific genes in driving squamous cell carcinomas. By describing the landscape of somatic targets in squamous cell lung cancer, we hope to crystallize the current understanding of potential targets, spur development of therapies that can have clinical impact, and underscore the importance of new discoveries in this field.

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    ABSTRACT: ABSTRACT The discovery of diverse driver mutations in lung cancer has heralded a new era of personalized medicine in thoracic oncology, with targeted therapies approved for specific subgroups of patients. The increasing number of patient subgroups that may respond to targeted therapy has resulted in a greater reliance upon effective and increasingly complex diagnostics, which must be interpreted in an interactive multidisciplinary forum. This review discusses the molecular diagnostics available and under development for established and emerging targets, and how these may be integrated into current treatment algorithms. The roles of the pulmonologist, interventional radiologist, thoracic surgeon and molecular pathologist are discussed, and their interactions with the medical oncologist, and/or thoracic surgeon and radiation oncologist in making individual treatment decisions.
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    ABSTRACT: The mechanisms of lung cancer are highly complex. Not only mRNA gene expression but also microRNAs, DNA methylation, and copy number variation (CNV) play roles in tumorigenesis. It is difficult to incorporate so much information into a single model that can comprehensively reflect all these lung cancer mechanisms. In this study, we analyzed the 129 TCGA (The Cancer Genome Atlas) squamous cell lung carcinoma samples with gene expression, microRNA expression, DNA methylation, and CNV data. First, we used variance inflation factor (VIF) regression to build the whole genome integrative network. Then, we isolated the lung cancer subnetwork by identifying the known lung cancer genes and their direct regulators. This subnetwork was refined by the Bayesian method, and the directed regulations among mRNA genes, microRNAs, methylations, and CNVs were obtained. The novel candidate key drivers in this refined subnetwork, such as the methylation of ARHGDIB and HOXD3, microRNA let-7a and miR-31, and the CNV of AGAP2, were identified and analyzed. On three large public available lung cancer datasets, the key drivers ARHGDIB and HOXD3 demonstrated significant associations with the overall survival of lung cancer patients. Our results provide new insights into lung cancer mechanisms.
    01/2015; 2015:358125. DOI:10.1155/2015/358125
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    ABSTRACT: Squamous cell carcinoma of the lung (SQCCL) remains a leading cause of cancer-related death. Unlike non-smoker adenocarcinoma of the lung, where highly efficient tyrosine kinase inhibitors are available for treating mutant EGFR or ALK-rearranged, no targetable biomarkers are available for SQCCL. The frequent and focal amplification of FGFR1 has generated great expectations in offering new therapeutical options in case of 16-22% of SQCCL patients. Broad 3q chromosome amplification is widely recognized as the most common chromosomal aberration found in SQCCL, where PIK3CA, SOX2, ACK1, PRKCI, TP63, PLD1, ECT2, and others genes are located. Although SOX2 has been postulated as a key regulator of basal stem cells transformation and tumor progression, it seems to confer a good prognosis in SQCCL. It is known that each patient might carry a different length of 3q chromosome amplicon. Thus, we suggest that the number and the biological importance of the genes spanned along each patient's 3q amplicon might help to explain inter-individual outcome variations of the disease and its potential predictive value, especially when relevant oncogenes such as those mentioned above are implicated. Currently, there is no clinical predictive data available from clinical trials. In this review, we have focused on the potential role of FGFR1 in SQCCL prognosis. Additionally, we have explored recently available public data on the comprehensive genomic characterization of SQCCL, in relation to the protein-coding genes that have a strong gene copy number - mRNA correlation in 3q chromosome, that were previously described as potential driver oncogenes or its modifiers in SQCCL.
    04/2013; 2(2):101-11. DOI:10.3978/j.issn.2218-6751.2013.03.05


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