PMID- 32664698
OWN - NLM
STAT- MEDLINE
DCOM- 20210226
LR  - 20210630
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 14
DP  - 2020 Jul 12
TI  - Unproductive Effects of ALK Gene Amplification and Copy Number Gain in 
      Non-Small-Cell Lung Cancer. ALK Gene Amplification and Copy Gain in NSCLC.
LID - 10.3390/ijms21144927 [doi]
LID - 4927
AB  - Background: The Anaplastic Lymphoma Kinase (ALK) gene is known to be affected by 
      several genetic alterations, such as rearrangement, amplification and point 
      mutation. The main goal of this study was to comprehensively analyze ALK 
      amplification (ALK-A) and ALK gene copy number gain (ALK-CNG) in a large cohort 
      of non-small-cell lung cancer (NSCLC) patients in order to evaluate the effects 
      on mRNA and protein expression. Methods: ALK locus number status was evaluated in 
      578 NSCLC cases by fluorescence in situ hybridization (FISH). In addition, ALK 
      immunohistochemistry and ALK mRNA in situ hybridization were performed. Results: 
      Out of 578 cases, 17 cases showed ALK-A. In addition, 14 cases presented ALK-CNG 
      and 72 cases presented chromosome 2 polyploidy. None of those carrying ALK-A and 
      -CNG showed either ALK immunohistochemical expression or ALK mRNA expression 
      through in situ hybridization. We observed a high frequency of extra copies of 
      the ALK gene. Conclusions: Our findings demonstrated that ALK-A is not involved 
      in mRNA production and consequently is not involved in protein production; these 
      findings support the hypothesis that ALK-A might not play a role in the 
      pathogenesis of NSCLC, underlining the absence of a specific clinical 
      application.
FAU - Zito Marino, Federica
AU  - Zito Marino F
AD  - Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, 
      University of Campania "L. Vanvitelli", 80138 Naples, Italy.
FAU - Botti, Gerardo
AU  - Botti G
AD  - Pathology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS 
      "Fondazione Pascale", 80131 Naples, Italy.
FAU - Aquino, Gabriella
AU  - Aquino G
AD  - Pathology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS 
      "Fondazione Pascale", 80131 Naples, Italy.
FAU - Ferrero, Stefano
AU  - Ferrero S
AD  - Division of Pathology, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, 
      20122 Milan, Italy.
AD  - Department of Biomedical, Surgical and Dental Sciences, University of Milan, 
      20100 Milan, Italy.
FAU - Gaudioso, Gabriella
AU  - Gaudioso G
AUID- ORCID: 0000-0002-3010-3268
AD  - Division of Pathology, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, 
      20122 Milan, Italy.
FAU - Palleschi, Alessandro
AU  - Palleschi A
AUID- ORCID: 0000-0003-4510-5167
AD  - Thoracic Surgery and Lung Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale 
      Maggiore Policlinico, 20122 Milan, Italy.
FAU - Rocco, Danilo
AU  - Rocco D
AD  - Department of Pulmonary Oncology, AORN Dei Colli Monaldi, 80131 Naples, Italy.
FAU - Salvi, Rosario
AU  - Salvi R
AD  - Thoracic Surgery Unit, AORN Dei Colli Monaldi, 80131 Naples, Italy.
FAU - Micheli, Maria Carolina
AU  - Micheli MC
AD  - Pathology Unit, AORN Dei Colli Monaldi, 80131 Naples, Italy.
FAU - Micheli, Pietro
AU  - Micheli P
AD  - Pathology Unit, AORN Dei Colli Monaldi, 80131 Naples, Italy.
FAU - Morabito, Alessandro
AU  - Morabito A
AD  - Thoracic Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, 
      IRCCS "Fondazione Pascale", 80131 Naples, Italy.
FAU - Rocco, Gaetano
AU  - Rocco G
AUID- ORCID: 0000-0003-4150-8604
AD  - Department of Thoracic Surgery, Memorial Sloan Kettering Cancer Center, New York, 
      NY 10065, USA.
FAU - Giordano, Antonio
AU  - Giordano A
AUID- ORCID: 0000-0002-5959-016X
AD  - Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 
      Siena, Italy.
AD  - Sbarro Health Research Organization, Philadelphia, PA 19122, USA.
FAU - De Cecio, Rossella
AU  - De Cecio R
AD  - Pathology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS 
      "Fondazione Pascale", 80131 Naples, Italy.
FAU - Franco, Renato
AU  - Franco R
AD  - Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, 
      University of Campania "L. Vanvitelli", 80138 Naples, Italy.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - Ricerca Corrente/Ministry Of Health/
PT  - Journal Article
DEP - 20200712
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
SB  - IM
MH  - Aged
MH  - Anaplastic Lymphoma Kinase/*genetics
MH  - Carcinoma, Non-Small-Cell Lung/*genetics
MH  - Chromosomes, Human, Pair 2/genetics
MH  - Female
MH  - *Gene Amplification
MH  - *Gene Dosage
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - In Situ Hybridization
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/*genetics
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Proteins/*genetics
MH  - Polyploidy
MH  - RNA, Messenger/biosynthesis/genetics
MH  - RNA, Neoplasm/biosynthesis/genetics
PMC - PMC7404032
OTO - NOTNLM
OT  - ALK
OT  - amplification
OT  - copy number gain
OT  - non-small-cell lung cancer
COIS- The authors declare no conflict of interest.
EDAT- 2020/07/16 06:00
MHDA- 2021/02/27 06:00
PMCR- 2020/07/01
CRDT- 2020/07/16 06:00
PHST- 2020/06/12 00:00 [received]
PHST- 2020/07/04 00:00 [revised]
PHST- 2020/07/07 00:00 [accepted]
PHST- 2020/07/16 06:00 [entrez]
PHST- 2020/07/16 06:00 [pubmed]
PHST- 2021/02/27 06:00 [medline]
PHST- 2020/07/01 00:00 [pmc-release]
AID - ijms21144927 [pii]
AID - ijms-21-04927 [pii]
AID - 10.3390/ijms21144927 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Jul 12;21(14):4927. doi: 10.3390/ijms21144927.