Genomic Copy Number Signatures Uncovered a Genetically Distinct Group from Adenocarcinoma and Squamous Cell Carcinoma in Non-Small Cell Lung Cancer

Han Kyeom Kim, Eunjung Lee, Ji Wook Moon, Xianfu Wang, Chungyeul Kim, Shibo Li, Bong Kyung Shin, Wonkyung Jung, Hyun Koo Kim, Ji-Yun Lee

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Summary 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.

Original languageEnglish
Pages (from-to)1111-1120
Number of pages10
JournalHuman Pathology
Volume46
Issue number8
DOIs
Publication statusPublished - 2015 Aug 1

Fingerprint

Non-Small Cell Lung Carcinoma
Squamous Cell Carcinoma
Adenocarcinoma
Genes
Comparative Genomic Hybridization
Cluster Analysis
Neoplasms
Carcinogenesis

Keywords

  • Adenocarcinoma
  • Array CGH
  • Copy number changes
  • NSCLC
  • Squamous cell carcinoma
  • TP63

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Genomic Copy Number Signatures Uncovered a Genetically Distinct Group from Adenocarcinoma and Squamous Cell Carcinoma in Non-Small Cell Lung Cancer. / Kim, Han Kyeom; Lee, Eunjung; Moon, Ji Wook; Wang, Xianfu; Kim, Chungyeul; Li, Shibo; Shin, Bong Kyung; Jung, Wonkyung; Kim, Hyun Koo ; Lee, Ji-Yun.

In: Human Pathology, Vol. 46, No. 8, 01.08.2015, p. 1111-1120.

Research output: Contribution to journalArticle

@article{3eabccf6da034c6f9906273baf2babe3,
title = "Genomic Copy Number Signatures Uncovered a Genetically Distinct Group from Adenocarcinoma and Squamous Cell Carcinoma in Non-Small Cell Lung Cancer",
abstract = "Summary 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.",
keywords = "Adenocarcinoma, Array CGH, Copy number changes, NSCLC, Squamous cell carcinoma, TP63",
author = "Kim, {Han Kyeom} and Eunjung Lee and Moon, {Ji Wook} and Xianfu Wang and Chungyeul Kim and Shibo Li and Shin, {Bong Kyung} and Wonkyung Jung and Kim, {Hyun Koo} and Ji-Yun Lee",
year = "2015",
month = "8",
day = "1",
doi = "10.1016/j.humpath.2015.04.009",
language = "English",
volume = "46",
pages = "1111--1120",
journal = "Human Pathology",
issn = "0046-8177",
publisher = "W.B. Saunders Ltd",
number = "8",

}

TY - JOUR

T1 - Genomic Copy Number Signatures Uncovered a Genetically Distinct Group from Adenocarcinoma and Squamous Cell Carcinoma in Non-Small Cell Lung Cancer

AU - Kim, Han Kyeom

AU - Lee, Eunjung

AU - Moon, Ji Wook

AU - Wang, Xianfu

AU - Kim, Chungyeul

AU - Li, Shibo

AU - Shin, Bong Kyung

AU - Jung, Wonkyung

AU - Kim, Hyun Koo

AU - Lee, Ji-Yun

PY - 2015/8/1

Y1 - 2015/8/1

N2 - Summary 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.

AB - Summary 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.

KW - Adenocarcinoma

KW - Array CGH

KW - Copy number changes

KW - NSCLC

KW - Squamous cell carcinoma

KW - TP63

UR - http://www.scopus.com/inward/record.url?scp=84937515157&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937515157&partnerID=8YFLogxK

U2 - 10.1016/j.humpath.2015.04.009

DO - 10.1016/j.humpath.2015.04.009

M3 - Article

VL - 46

SP - 1111

EP - 1120

JO - Human Pathology

JF - Human Pathology

SN - 0046-8177

IS - 8

ER -