The ACIN1 gene is hypermethylated in early stage lung adenocarcinoma.
OBJECTIVE
In recent years, many studies have performed genome-wide searching for differentially methylated genes in cancer. We hypothesized that characteristic aberrant hypermethylation of CpG islands of certain genes may exist in the early stages of lung adenocarcinoma and that such alterations may be useful in the detection and treatment of early lung adenocarcinoma.


METHODS
A pair of immortalized cell lines originating from atypical adenomatous hyperplasia (PL16T) and from the resected end of the bronchus of the same patient (PL16B) was searched for aberrantly and differentially hypermethylated DNA fragments by a combination of the methylated CpG island amplification and suppression subtractive hybridization methods.


RESULTS
From 229 clones, we selected 15 fragments that had a genomic region meeting the criteria for a CpG island. We identified a gene, apoptotic chromatin condensation inducer 1 (ACIN1), that was hypermethylated in PL16T. A higher frequency of hypermethylation at a locus at the 5': end of the DNA fragment isolated from the ACIN1 gene was found in small-sized adenocarcinoma (2 cm or less) (30/37, 81%) compared with normal lung tissue (9/37, 24%, p < 0.05). Interestingly, hypermethylation of ACIN1 was detected relatively frequently in the normal counterpart of adenocarcinoma without bronchioloalveolar carcinoma (BAC) component (7/16, 44%), but was rare in the normal counterpart of adenocarcinoma with BAC component (2/21, 10%, P < 0.05).


CONCLUSIONS
We found hypermethylation of the ACIN1 gene in early stage lung adenocarcinoma. The role of methylation status in the development and malignant transformation of lung adenocarcinoma requires clarification.
Shu
Yujian
Y
Department of Pathology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
Iijima
Tatsuo
T
Sun
Weihong
W
Kano
Junko
J
Ishiyama
Tadashi
T
Okubo
Chigusa
C
Anami
Yoichi
Y
Tanaka
Ryota
R
Fukai
Shimao
S
Noguchi
Masayuki
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
C121310:ACIN1 protein, human; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009687:Nuclear Proteins