Identification of novel candidate target genes, including EPHB3, MASP1 and SST at 3q26.2-q29 in squamous cell carcinoma of the lung.
BACKGROUND
The underlying genetic alterations for squamous cell carcinoma (SCC) and adenocarcinoma (AC) carcinogenesis are largely unknown.


METHODS
High-resolution array- CGH was performed to identify the differences in the patterns of genomic imbalances between SCC and AC of non-small cell lung cancer (NSCLC).


RESULTS
On a genome-wide profile, SCCs showed higher frequency of gains than ACs (p = 0.067). More specifically, statistically significant differences were observed across the histologic subtypes for gains at 2q14.2, 3q26.2-q29, 12p13.2-p13.33, and 19p13.3, as well as losses at 3p26.2-p26.3, 16p13.11, and 17p11.2 in SCC, and gains at 7q22.1 and losses at 15q22.2-q25.2 occurred in AC (P < 0.05). The most striking difference between SCC and AC was gains at the 3q26.2-q29, occurring in 86% (19/22) of SCCs, but in only 21% (3/14) of ACs. Many significant genes at the 3q26.2-q29 regions previously linked to a specific histology, such as EVI1,MDS1, PIK3CA and TP73L, were observed in SCC (P < 0.05). In addition, we identified the following possible target genes (> 30% of patients) at 3q26.2-q29: LOC389174 (3q26.2),KCNMB3 (3q26.32),EPHB3 (3q27.1), MASP1 and SST (3q27.3), LPP and FGF12 (3q28), and OPA1,KIAA022,LOC220729, LOC440996,LOC440997, and LOC440998 (3q29), all of which were significantly targeted in SCC (P < 0.05). Among these same genes, high-level amplifications were detected for the gene, EPHB3, at 3q27.1, and MASP1 and SST, at 3q27.3 (18, 18, and 14%, respectively). Quantitative real time PCR demonstrated array CGH detected potential candidate genes that were over expressed in SCCs.


CONCLUSIONS
Using whole-genome array CGH, we have successfully identified significant differences and unique information of chromosomal signatures prevalent between the SCC and AC subtypes of NSCLC. The newly identified candidate target genes may prove to be highly attractive candidate molecular markers for the classification of NSCLC histologic subtypes, and could potentially contribute to the pathogenesis of the squamous cell carcinoma of the lung.
Kang
Ji Un
JU
Department of Pathology, Columbia University Medical Center, New York, NY, USA. ju2497@gmail.com
Koo
Sun Hoe
SH
Kwon
Kye Chul
KC
Park
Jong Woo
JW
Kim
Jin Man
JM
D015415:Biomarkers / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002875:Chromosomes / Q000648:ultrastructure; D022202:Chromosomes, Artificial, Bacterial; D002893:Chromosomes, Human, Pair 3; D020869:Gene Expression Profiling / Q000379:methods; D015894:Genome, Human; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D036223:Receptor, EphB3 / Q000235:genetics*; D013004:Somatostatin / Q000235:genetics*
D015415:Biomarkers; D013004:Somatostatin; D036223:Receptor, EphB3; C084067:MASP1 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases