PMID- 22672386
OWN - NLM
STAT- MEDLINE
DCOM- 20130117
LR  - 20240418
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 12
DP  - 2012 Jun 6
TI  - Expression of proto-oncogene KIT is up-regulated in subset of human meningiomas.
PG  - 212
LID - 10.1186/1471-2407-12-212 [doi]
AB  - BACKGROUND: KIT is a proto-oncogene involved in diverse neoplastic processes. 
      Aberrant kinase activity of the KIT receptor has been targeted by tyrosine kinase 
      inhibitor (TKI) therapy in different neoplasias. In all the earlier studies, KIT 
      expression was reported to be absent in meningiomas. However, we observed KIT 
      mRNA expression in some meningioma cases. This prompted us to undertake its 
      detailed analyses in meningioma tissues resected during 2008-2009. METHODS: Tumor 
      tissues and matched peripheral blood samples collected from meningioma patients 
      were used for detailed molecular analyses. KIT expression was ascertained 
      immunohistochemically and validated by immunoblotting. KIT and KITLG transcript 
      levels were discerned by reverse transcription quantitative real-time PCR 
      (RT-qPCR). Similarly, KIT amplification and allele loss were assessed by 
      quantitative real-time (qPCR) and validated by fluorescence in situ hybridization 
      (FISH) on the neoplastic tissues. Possible alterations of the gene at the 
      nucleotide level were analyzed by sequencing. RESULTS: Contrary to earlier 
      reports, KIT expression, was detected immunohistochemically in 20.6% meningioma 
      cases (n = 34). Receptor (KIT) and ligand (KITLG) transcripts monitored by 
      RT-qPCR were found to co-express (p = 0.048) in most of the KIT immunopositive 
      tumors. 1/7 KIT positive meningiomas showed allele loss corroborated by reduced 
      FISH signal in the corresponding neoplastic tissue. Sequence analysis of KIT 
      showed M541L substitution in exon 10, in one of the immunopositive cases. 
      However, its biological consequence remains to be uncovered. CONCLUSIONS: This 
      study clearly demonstrates KIT over-expression in the human meningiomas. The data 
      suggest that up-regulated KIT transcription (p < 0.001), instead of gene 
      amplification (p > 0.05), is a likely mechanism responsible for altered KIT 
      expression. Thus, KIT is a potential candidate for detailed investigation in the 
      context of meningioma pathogenesis.
FAU - Saini, Masum
AU  - Saini M
AD  - Molecular Genetics Laboratory, National Institute of Immunology, Aruna Asaf Ali 
      Marg, New Delhi 110067, India.
FAU - Jha, Ajaya Nand
AU  - Jha AN
FAU - Abrari, Andleeb
AU  - Abrari A
FAU - Ali, Sher
AU  - Ali S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120606
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Stem Cell Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Base Sequence
MH  - Exons
MH  - Female
MH  - Gene Dosage
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Male
MH  - Meningeal Neoplasms/*genetics/pathology
MH  - Meningioma/*genetics/pathology
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins c-kit/chemistry/*genetics/metabolism
MH  - Stem Cell Factor/genetics/metabolism
PMC - PMC3443037
EDAT- 2012/06/08 06:00
MHDA- 2013/01/18 06:00
PMCR- 2012/06/06
CRDT- 2012/06/08 06:00
PHST- 2011/10/29 00:00 [received]
PHST- 2012/06/06 00:00 [accepted]
PHST- 2012/06/08 06:00 [entrez]
PHST- 2012/06/08 06:00 [pubmed]
PHST- 2013/01/18 06:00 [medline]
PHST- 2012/06/06 00:00 [pmc-release]
AID - 1471-2407-12-212 [pii]
AID - 10.1186/1471-2407-12-212 [doi]
PST - epublish
SO  - BMC Cancer. 2012 Jun 6;12:212. doi: 10.1186/1471-2407-12-212.