Genomic copy number alterations associated with the early brain metastasis of non-small cell lung cancer

Lee,Hye Won; Seol,Ho  Jun; Choi,Yoon-La; Ju,Hyun  Jung; Joo,Kyeung   Min; Ko,Young-Hyeh; Lee,Jung-Il; Nam,Do-Hyun

doi:10.3892/ijo.2012.1663

Genomic copy number alterations associated with the early brain metastasis of non-small cell lung cancer

Authors:
- Hye Won Lee
- Ho Jun Seol
- Yoon-La Choi
- Hyun Jung Ju
- Kyeung Min Joo
- Young-Hyeh Ko
- Jung-Il Lee
- Do-Hyun Nam
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Affiliations: Cancer Stem Cell Research Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea, Department of Pathology, Institute for Refractory Cancer Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea, Department of Anatomy, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea, Department of Neurosurgery, Institute for Refractory Cancer Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea
Published online on: October 15, 2012 https://doi.org/10.3892/ijo.2012.1663
Pages: 2013-2020

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Abstract

Frequent early development of systemic metastasis leads to unfavourable clinical prognosis of non-small cell lung cancer (NSCLC). Although brain metastasis (BM) contributes significantly to morbidity and mortality of NSCLC, relevant driver mechanisms are largely unknown. To elucidate genetic alterations associated with early BM of NSCLC, we retrospectively collected 18 NSCLC cases with BM [12 adenocarcinomas (ADC) and 6 squamous cell carcinomas (SQCC)] whose surgical tissues of both primary and brain metastatic tumors were preserved as formaldehyde-fixed and paraffin-embedded (FFPE) pathological samples. When chromosomal copy number alterations (CNA) of those FFPE samples were analysed by the Molecular Inversion Probe (MIP) technology, the most frequent CNAs detected in primary lung ADCs were gains of 3q, 5p, 5q, 6p, 8q, 9p, 11p, 15q, 17q and losses of 10q and 22q whereas primary lung SQCCs revealed gains in 4q and 12q and loss in 9q. In particular, when comparative MIP was performed in primary 12 ADCs depending on the pattern of BM to uncover predetermining signatures that can predict the risk of BM, selectively amplified regions of primary lung ADCs (5q35, 10q23 and 17q23-24) were identified as significantly associated with the development of early BM within 3 months after first diagnosis of primary tumors. Those regions harbour several candidate genes including NeurL1B, ACTA2, FAS and ICAM2. Although more validation is needed, the genetic signatures elucidated in this study help to identify useful molecular markers deﬁning an NSCLC patient subgroup at risk of early BM, guiding therapeutic decisions.

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