PMID- 31138176
OWN - NLM
STAT- MEDLINE
DCOM- 20191125
LR  - 20201218
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 19
IP  - 1
DP  - 2019 May 28
TI  - CDKN2A copy number and p16 expression in malignant pleural mesothelioma in 
      relation to asbestos exposure.
PG  - 507
LID - 10.1186/s12885-019-5652-y [doi]
LID - 507
AB  - BACKGROUND: Deletion of the CDKN2A locus is centrally involved in the development 
      of several malignancies. In malignant pleural mesothelioma (MPM), it is one of 
      the most frequently reported genomic alteration. MPM is strongly associated with 
      a patients' asbestos exposure. However, the status of CDKN2A and the expression 
      of the corresponding protein, p16, in relation to MPM patient's asbestos exposure 
      is poorly known. Copy number alterations in 2p16, 9q33.1 and 19p13 have earlier 
      been shown to accumulate in lung cancer in relation to asbestos exposure but 
      their status in MPM is unclear. METHODS: We studied DNA copy numbers for CDKN2A 
      using fluorescence in situ hybridization (FISH) and p16 expression by 
      immunohistochemistry (IHC) in 92 MPM patients, 75 of which with known asbestos 
      exposure status. We also studied, in MPM, copy number alterations in 2p16, 9q33.1 
      and 19p13 by FISH. RESULTS: We were unable to detect an association between p16 
      expression and pulmonary asbestos fiber count in MPM tumor cells. However, 
      significantly more MPM patients with high pulmonary asbestos fiber count (> 1 
      million fibers per gram [f/g]) had stromal p16 immunoreactivity than MPM of 
      patients with low exposure (</= 0.5 million f/g) (51.4% vs 16.7%; p = 0.035, 
      Chi-Square). We found that an abnormal copy number of CDKN2A in MPM tumor cells 
      associated with a high pulmonary asbestos fiber count (p = 0.044, Fisher's Exact 
      test, two-tailed). In contrast to our earlier findings in asbestos associated 
      lung cancer, DNA copy number changes in 2p16, 9q33 and 19p13 were not frequent in 
      MPM although single cases with variable copy numbers on those regions were seen. 
      CONCLUSIONS: We found two instances where the gene locus CDKN2A or its 
      corresponding protein expression, is associated with high asbestos exposure 
      levels. This suggests that there may be biological differences between the 
      mesotheliomas with high pulmonary asbestos fiber count and those with low fiber 
      count.
FAU - Kettunen, Eeva
AU  - Kettunen E
AUID- ORCID: 0000-0001-5769-3010
AD  - Research and Service Centre for Occupational Safety, Finnish Institute of 
      Occupational Health, PO Box 40, FI-00032 Tyoterveyslaitos, Helsinki, Finland. 
      eeva.kettunen@ttl.fi.
FAU - Savukoski, Sauli
AU  - Savukoski S
AD  - Research and Service Centre for Occupational Safety, Finnish Institute of 
      Occupational Health, PO Box 40, FI-00032 Tyoterveyslaitos, Helsinki, Finland.
FAU - Salmenkivi, Kaisa
AU  - Salmenkivi K
AD  - Department of Pathology, University of Helsinki, and HUSLAB, Helsinki University 
      Hospital, 00029 HUS, Helsinki, Finland.
FAU - Bohling, Tom
AU  - Bohling T
AD  - Department of Pathology, University of Helsinki, and HUSLAB, Helsinki University 
      Hospital, 00029 HUS, Helsinki, Finland.
FAU - Vanhala, Esa
AU  - Vanhala E
AD  - Research and Service Centre for Occupational Safety, Finnish Institute of 
      Occupational Health, PO Box 40, FI-00032 Tyoterveyslaitos, Helsinki, Finland.
FAU - Kuosma, Eeva
AU  - Kuosma E
AD  - Research and Service Centre for Occupational Safety, Finnish Institute of 
      Occupational Health, PO Box 40, FI-00032 Tyoterveyslaitos, Helsinki, Finland.
FAU - Anttila, Sisko
AU  - Anttila S
AD  - Research and Service Centre for Occupational Safety, Finnish Institute of 
      Occupational Health, PO Box 40, FI-00032 Tyoterveyslaitos, Helsinki, Finland.
AD  - Department of Pathology, University of Helsinki, and HUSLAB, Helsinki University 
      Hospital, 00029 HUS, Helsinki, Finland.
FAU - Wolff, Henrik
AU  - Wolff H
AD  - Research and Service Centre for Occupational Safety, Finnish Institute of 
      Occupational Health, PO Box 40, FI-00032 Tyoterveyslaitos, Helsinki, Finland.
LA  - eng
GR  - 115372/Terveyden Tutkimuksen Toimikunta/
GR  - 109003/Tyosuojelurahasto/
PT  - Journal Article
DEP - 20190528
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (CDKN2A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 1332-21-4 (Asbestos)
SB  - IM
MH  - Aged
MH  - Asbestos/*adverse effects
MH  - Chromosomes, Human/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p16/*genetics/*metabolism
MH  - *DNA Copy Number Variations
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/chemically induced/genetics/*metabolism
MH  - Male
MH  - Mesothelioma/chemically induced/genetics/*metabolism
MH  - Mesothelioma, Malignant
MH  - Middle Aged
MH  - Stromal Cells/metabolism
MH  - Tissue Array Analysis
PMC - PMC6537412
OTO - NOTNLM
OT  - Asbestos exposure
OT  - CDKN2A
OT  - Malignant pleural mesothelioma
OT  - Tumor stroma
OT  - p16
COIS- The authors declare that they have no competing interests.
EDAT- 2019/05/30 06:00
MHDA- 2019/11/26 06:00
PMCR- 2019/05/28
CRDT- 2019/05/30 06:00
PHST- 2018/11/09 00:00 [received]
PHST- 2019/04/29 00:00 [accepted]
PHST- 2019/05/30 06:00 [entrez]
PHST- 2019/05/30 06:00 [pubmed]
PHST- 2019/11/26 06:00 [medline]
PHST- 2019/05/28 00:00 [pmc-release]
AID - 10.1186/s12885-019-5652-y [pii]
AID - 5652 [pii]
AID - 10.1186/s12885-019-5652-y [doi]
PST - epublish
SO  - BMC Cancer. 2019 May 28;19(1):507. doi: 10.1186/s12885-019-5652-y.