Abstract

BackgroundSOX7 is a transcription factor belonging to the SOX family. Its role in lung cancer is unknown.MethodsIn this study, whole genomic copy number analysis was performed on a series of non-small cell lung cancer (NSCLC) cell lines and samples from individuals with epidermal growth factor receptor (EGFR) mutations using a SNP-Chip platform. SOX7 was measured in NSCLC samples and cell lines, and forced expressed in one of these lines.ResultsA notable surprise was that the numerous copy number (CN) changes observed in samples of Asian, non-smoking EGFR mutant NSCLC were nearly the same as those CN alterations seen in a large collection of NSCLC from The Cancer Genome Atlas which is presumably composed of predominantly Caucasians who often smoked. However, four regions had CN changes fairly unique to the Asian EGFR mutant group. We also examined CN changes in NSCLC lines. The SOX7 gene was homozygously deleted in one (HCC2935) of 10 NSCLC cell lines and heterozygously deleted in two other NSCLC lines. Expression of SOX7 was significantly downregulated in NSCLC cell lines (8/10, 80%) and a large collection of NSCLC samples compared to matched normal lung (57/62, 92%, p= 0.0006). Forced-expression of SOX7 in NSCLC cell lines markedly reduced their cell growth and enhanced their apoptosis.ConclusionThese data suggest that SOX7 is a novel tumor suppressor gene silenced in the majority of NSCLC samples.

Highlights

  • Lung cancer is the leading cause of cancer-related death in the world

  • An example is the use of Gefitinib for patients whose non-small cell lung cancer (NSCLC) has an epidermal growth factor receptor (EGFR) mutation in either exon 19 or 21

  • Whole genomic copy number analysis using high resolution SNP-Chips in NSCLC samples and cell lines Initially, genomic alterations were examined in a small sample set of Asians with NSCLC with EGFR mutations

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Summary

Introduction

Lung cancer is the leading cause of cancer-related death in the world. An example is the use of Gefitinib for patients whose non-small cell lung cancer (NSCLC) has an epidermal growth factor receptor (EGFR) mutation in either exon 19 or 21. SOX7 is a member of the SOX (SRY-related high mobility group box) transcription factors [1]. This protein, together with SOX17 and SOX18, comprises the SOX F subgroup [2] and helps mediate various developmental processes including a role in the regulation of hematopoiesis [3], cardiogenesis [4], vasculogenesis [5,6], endoderm differentiation [7] and. Its role in lung cancer is unknown

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