title: Genomic Alterations in the RB Pathway Indicate Prognostic Outcomes of Early-Stage Lung Adenocarcinoma.
abstract: OBJECTIVE
  To better understand the complete genomic architecture of lung adenocarcinoma.
  
  
  METHODS
  We used array experiments to determine copy number variations and sequenced the complete exomes of the 247 lung adenocarcinoma tumor samples along with matched normal cells obtained from the same patients. Fully annotated clinical data were also available, providing an unprecedented opportunity to assess the impact of genomic alterations on clinical outcomes.
  
  
  RESULTS
  We discovered that genomic alternations in the RB pathway are associated with significantly shorter disease-free survival in early-stage lung adenocarcinoma patients. This association was also observed in our independent validation cohort. The current treatment guidelines for early-stage lung adenocarcinoma patients recommend follow-up without adjuvant therapy after complete resection, except for high-risk patients. However, our findings raise the interesting possibility that additional clinical interventions might provide medical benefits to early-stage lung adenocarcinoma patients with genomic alterations in the RB pathway. When examining the association between genomic mutation and histologic subtype, we uncovered the characteristic genomic signatures of various histologic subtypes. Notably, the solid and the micropapillary subtypes demonstrated great diversity in the mutated genes, while the mucinous subtype exhibited the most unique landscape. This suggests that a more tailored therapeutic approach should be used to treat patients with lung adenocarcinoma.
  
  
  CONCLUSIONS
  Our analysis of the genomic and clinical data for 247 lung adenocarcinomas should help provide a more comprehensive genomic portrait of lung adenocarcinoma, define molecular signatures of lung adenocarcinoma subtypes, and lead to the discovery of useful prognostic markers that could be used in personalized treatments for early-stage lung adenocarcinoma patients.
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul National University, Seoul, South Korea. School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea.
authors.forename: Seongmin
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Hyeong Ryul
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Chang Ohk
authors.initials: CO
authors.lastname: Sung
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul National University, Seoul, South Korea. School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea.
authors.forename: Jongkyu
authors.initials: J
authors.lastname: Kim
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul National University, Seoul, South Korea. School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea.
authors.forename: Sukjun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. Center for Cancer Genome Discovery, Asan Institute for Life Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. Department of Bioinformatics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Ahn
authors.affiliation: Department of Pulmonology and Medical Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Chang-min
authors.initials: CM
authors.lastname: Choi
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Chun
authors.affiliation: Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Choi
authors.affiliation: Center for Cancer Genome Discovery, Asan Institute for Life Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Sang-We
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Yong-Hee
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Asan Institute for Life Sciences, Seoul, South Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Joon Seon
authors.initials: JS
authors.lastname: Song
authors.affiliation: Department of Bioinformatics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Deokhoon
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Bioinformatics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, South Korea.
authors.forename: Farhan
authors.initials: F
authors.lastname: Haq
authors.affiliation: Department of Bioinformatics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: DNA Link, Inc., Asan Institute for Life Sciences, Seoul, South Korea.
authors.forename: Jong-eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: DNA Link, Inc., Asan Institute for Life Sciences, Seoul, South Korea.
authors.forename: Wang-rim
authors.initials: WR
authors.lastname: Jung
authors.affiliation: DNA Link, Inc., Asan Institute for Life Sciences, Seoul, South Korea.
authors.forename: Hye Yoon
authors.initials: HY
authors.lastname: Jang
authors.affiliation: DNA Link, Inc., Asan Institute for Life Sciences, Seoul, South Korea.
authors.forename: Eunho
authors.initials: E
authors.lastname: Yang
authors.affiliation: The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut. Department of Graduate Studies, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Eunsil
authors.initials: E
authors.lastname: Yu
authors.affiliation: Department of Pathology, College of Medicine, Hanyang University, Seoul, South Korea. baek@snu.ac.kr gkong@hanyang.ac.kr jangsejin@amc.seoul.kr.
authors.forename: Gu
authors.initials: G
authors.lastname: Kong
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul National University, Seoul, South Korea. School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea. Bioinformatics Institute, Seoul National University, Seoul, South Korea. baek@snu.ac.kr gkong@hanyang.ac.kr jangsejin@amc.seoul.kr.
authors.forename: Daehyun
authors.initials: D
authors.lastname: Baek
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. Center for Cancer Genome Discovery, Asan Institute for Life Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. baek@snu.ac.kr gkong@hanyang.ac.kr jangsejin@amc.seoul.kr.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000235:genetics*
chemical_list: C530104:CCND1 protein, human; D016160:Retinoblastoma Protein; D019938:Cyclin D1