title: Genomic Copy Number Signatures Uncovered a Genetically Distinct Group from Adenocarcinoma and Squamous Cell Carcinoma in Non-Small Cell Lung Cancer.
abstract: Adenocarcinoma (AC) and squamous cell carcinoma (SCC) of non-small cell lung carcinoma (NSCLC) have different clinical presentations, morphologies, treatments, and prognoses. Recent studies suggested that fundamental genetic alterations related to carcinogenesis of each tumor type may be different. In this study, we investigated the genomic alterations of 47 primary NSCLC samples (22 ACs and 25 SCCs) as well as the corresponding normal tissue using array comparative genomic hybridization. Frequent copy number alterations (CNAs), which were identified in more than 68% of all of the cases, were evaluated in each subtype (SCC and AC), and a CNA signature was established. Among these CNAs, 37 genes from the SCCs and 15 genes from the ACs were located in a region of gain, and 4 genes from the SCCs and 13 genes from the ACs were located in a region of loss. The most frequent gain was located on 3q26-29 including the gene TP63 in SCCs and 7q11.23 and 7q36.3 in ACs. Moreover, we identified 3 genetically distinct groups (group I [16 SCC] with CNA signature of SCC; group II [7 SCC + 8 AC], which has a genetically distinctive CNA signature from SCC and AC; and group III [2 SCC + 14 AC] with CNA signature of AC) by gene clustering extracted from CNAs, which are associated with a prognosis. The present study contributed to the molecular characterization of AC and SCC of NSCLC and showed a subtype of tumor that has a unique genetic CNA signature. However, further study about the significance of these 3 distinct groups and their usefulness as a diagnostic marker of identified CNAs is necessary.
authors.affiliation: Department of Pathology, College of Medicine, Korea University Guro Hospital, Seoul, 152-703 South Korea; Department of Pathology, College of Medicine, Korea University, Seoul, 136-705 South Korea.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Pathology, College of Medicine, Korea University, Seoul, 136-705 South Korea.
authors.forename: Ji Wook
authors.initials: JW
authors.lastname: Moon
authors.affiliation: Department of Pediatrics, College of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Xianfu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology, College of Medicine, Korea University Guro Hospital, Seoul, 152-703 South Korea.
authors.forename: Chungyeul
authors.initials: C
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, College of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Shibo
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pathology, College of Medicine, Korea University Guro Hospital, Seoul, 152-703 South Korea; Department of Pathology, College of Medicine, Korea University, Seoul, 136-705 South Korea.
authors.forename: Bong Kyung
authors.initials: BK
authors.lastname: Shin
authors.affiliation: Department of Pathology, College of Medicine, Korea University Guro Hospital, Seoul, 152-703 South Korea.
authors.forename: Wonkyung
authors.initials: W
authors.lastname: Jung
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, College of Medicine, Korea University Guro Hospital, Seoul, 152-703 South Korea.
authors.forename: Hyun Koo
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Medicine, Korea University Guro Hospital, Seoul, 152-703 South Korea; Department of Pathology, College of Medicine, Korea University, Seoul, 136-705 South Korea. Electronic address: sswords@naver.com.
authors.forename: Han Kyeom
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Medicine, Korea University, Seoul, 136-705 South Korea. Electronic address: jiyun-lee@korea.ac.kr.
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000145:classification / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D046888:Tissue Array Analysis; D059467:Transcriptome / Q000235:genetics
keywords: Adenocarcinoma; Array CGH; Copy number changes; NSCLC; Squamous cell carcinoma; TP63