PMID- 30773851
OWN - NLM
STAT- MEDLINE
DCOM- 20200507
LR  - 20210109
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Linking)
VI  - 8
IP  - 4
DP  - 2019 Apr
TI  - Retinoblastoma mutation predicts poor outcomes in advanced non small cell lung 
      cancer.
PG  - 1459-1466
LID - 10.1002/cam4.2023 [doi]
AB  - The retinoblastoma gene (RB1) encodes the retinoblastoma (RB) pocket protein that 
      plays an important role in cell cycle progression. Here we determine the 
      frequency and prognostic significance of RB1 mutation in non small cell lung 
      cancer (NSCLC), restricting inclusion to Stage III and IV patients with linked 
      genomic and clinical data. The primary outcome was median overall survival (OS). 
      We identified RB1 mutation in 8.2% of NSCLC patients. The median OS for wild-type 
      (wt) RB1 was 28.3 months vs 8.3 months for mutant RB1 (Hazard Ratio = 2.59, 
      P = 0.002). Of special interest, RB1 mutation also correlated with lack of 
      response to immunotherapy. Our study focused on RB1 mutation in locally advanced 
      and advanced non small cell lung cancer to better facilitate comparisons with 
      small cell lung cancer (SCLC). In our SCLC cohort, RB1 mutation was identified in 
      75% of patients and wt RB1 was associated with significantly shorter OS 
      (P = 0.002). The different outcomes of RB1 mutation observed among lung cancer 
      subtypes suggest a more complicated mechanism than simple regulation of cell 
      cycle or response to chemotherapy.
CI  - (c) 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Bhateja, Priyanka
AU  - Bhateja P
AD  - Department of Hematology and Oncology, Case Western Reserve University, 
      University Hospitals Seidman Cancer Center, Cleveland, Ohio.
FAU - Chiu, Michelle
AU  - Chiu M
AD  - School of Medicine, Case Western Reserve University, Cleveland, Ohio.
FAU - Wildey, Gary
AU  - Wildey G
AUID- ORCID: 0000-0001-7105-1313
AD  - School of Medicine, Case Western Reserve University, Cleveland, Ohio.
FAU - Lipka, Mary Beth
AU  - Lipka MB
AD  - Department of Hematology and Oncology, University Hospitals Seidman Cancer 
      Center, Cleveland, Ohio.
FAU - Fu, Pingfu
AU  - Fu P
AD  - Department of Population and Quantitative Health Sciences, Case Western Reserve 
      University, Cleveland, Ohio.
FAU - Yang, Michael Chiu Lee
AU  - Yang MCL
AD  - Department of Pathology, University Hospitals Cleveland Medical Center, 
      Cleveland, Ohio.
FAU - Ardeshir-Larijani, Fatemeh
AU  - Ardeshir-Larijani F
AD  - Department of Internal Medicine, University Hospitals Cleveland Medical Center, 
      Cleveland, Ohio.
FAU - Sharma, Neelesh
AU  - Sharma N
AD  - Department of Biomedical Research, Novartis Pharmaceuticals Corporation, East 
      Hanover, New Jersey.
FAU - Dowlati, Afshin
AU  - Dowlati A
AD  - Department of Hematology and Oncology, Case Western Reserve University, 
      University Hospitals Seidman Cancer Center, Cleveland, Ohio.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190217
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (RB1 protein, human)
RN  - 0 (Retinoblastoma Binding Proteins)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents, Immunological/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy/*genetics/pathology
MH  - Diagnosis, Differential
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/drug therapy/*genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Mutation Rate
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Retinoblastoma Binding Proteins/*genetics
MH  - Small Cell Lung Carcinoma/drug therapy/*genetics/pathology
MH  - Survival Analysis
MH  - Treatment Outcome
MH  - Ubiquitin-Protein Ligases/*genetics
PMC - PMC6488103
OTO - NOTNLM
OT  - genomics
OT  - immunotherapy
OT  - non small cell lung cancer
OT  - response
OT  - retinoblastoma
OT  - small cell lung cancer
COIS- None declared.
EDAT- 2019/02/19 06:00
MHDA- 2020/05/08 06:00
PMCR- 2019/02/17
CRDT- 2019/02/19 06:00
PHST- 2018/10/09 00:00 [received]
PHST- 2019/01/07 00:00 [revised]
PHST- 2019/01/16 00:00 [accepted]
PHST- 2019/02/19 06:00 [pubmed]
PHST- 2020/05/08 06:00 [medline]
PHST- 2019/02/19 06:00 [entrez]
PHST- 2019/02/17 00:00 [pmc-release]
AID - CAM42023 [pii]
AID - 10.1002/cam4.2023 [doi]
PST - ppublish
SO  - Cancer Med. 2019 Apr;8(4):1459-1466. doi: 10.1002/cam4.2023. Epub 2019 Feb 17.