Genomic copy number alterations associated with the early brain metastasis             of non-small cell lung cancer.
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.
Cancer Stem Cell Research Center, Sungkyunkwan University School                     of Medicine, Seoul 135-710, Republic of Korea.
Hye Won
HW
Lee
Ho Jun
HJ
Seol
Yoon-La
YL
Choi
Hyun Jung
HJ
Ju
Kyeung Min
KM
Joo
Young-Hyeh
YH
Ko
Jung-Il
JI
Lee
Do-Hyun
DH
Nam
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis