PMID- 20444664
OWN - NLM
STAT- MEDLINE
DCOM- 20101102
LR  - 20210208
IS  - 1877-783X (Electronic)
IS  - 1877-7821 (Linking)
VI  - 34
IP  - 4
DP  - 2010 Aug
TI  - Alterations in p16 and p53 genes and chromosomal findings in patients with lung 
      cancer: fluorescence in situ hybridization and cytogenetic studies.
PG  - 472-7
LID - 10.1016/j.canep.2010.03.018 [doi]
AB  - BACKGROUND: Chromosomal aberrations and instability of gene(s) are two factors 
      related to the genetic instability of cancer cells. A loss of the 
      tumor-suppressor function of the genes p16 and p53 is the most common event 
      leading to the development of human cancers. Carcinoma of the lung is the leading 
      cause of cancer deaths in the world. Chromosomal abnormalities in lung cancer may 
      provide a valuable clue to the identification of target loci and culminate in a 
      successful search for the major genes. The aim of this study was to investigate 
      (i) alterations of the p16 and p53 genes and (ii) chromosomal aberrations in 
      patients with small cell and non-small cell lung cancer by fluorescence in situ 
      hybridization (FISH) and cytogenetic studies. We carried out cytogenetic analysis 
      by Giemsa-banding in 18 cases. FISH probes for the p16 and p53 genes were also 
      used on interphase nuclei to screen the alterations in these genes in lung cancer 
      (LC). RESULTS: We observed a high frequency of losses of the p16 - in 8/18 (44%) 
      - and p53 - in 7/18 (39%) - genes in the cases with LC. A total of 18 patients 
      showed predominantly numerical and structural aberrations. Among these two types, 
      structural aberrations predominated and usually consisted of deletions, breaks, 
      and fragilities in various chromosomes. Both structural and numerical changes 
      were observed in almost all patients. Chromosomes 3 and 1 were found to be most 
      frequently involved in structural abnormalities, followed by chromosomes 6, 9, 
      and 8. Autosomal aneuploidies were also observed to be the most frequent 
      (chromosomes 22, 19, 18, 20, 9, and 17), followed by those of the X and Y 
      chromosomes. The expression of fragile sites was also found to be significantly 
      higher in seven chromosomal regions: 3p14, 1q21, 1q12, 6q26, 9q13, 8q22, and 
      8q24. CONCLUSION: Our data confirmed that DNA damage and genomic instability may 
      be factors contributing to the mutation profile and development of lung cancer. 
      The patients who developed lung cancer showed a high frequency of loss of both 
      p16 and p53, in addition to chromosomal aberrations. Tobacco could be a major 
      carcinogenic factor in lung-cancer progression. The loss of p16 and p53, and 
      increased incidence of autosomal aneuploidy and chromatid breaks, along with 
      other chromosomal alterations, can contribute to the progression of the disease.
FAU - Demirhan, Osman
AU  - Demirhan O
AD  - Department of Medical Biology and Genetics, Cukurova University, 01330 
      Balcali-Adana, Turkey. osdemir@cu.edu.tr
FAU - Tastemir, Deniz
AU  - Tastemir D
FAU - Hasturk, Serap
AU  - Hasturk S
FAU - Kuleci, Sedat
AU  - Kuleci S
FAU - Hanta, Ismail
AU  - Hanta I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100504
PL  - Netherlands
TA  - Cancer Epidemiol
JT  - Cancer epidemiology
JID - 101508793
RN  - 0 (CDKN2A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/pathology
MH  - *Chromosome Aberrations
MH  - Chromosomes, Human/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p16
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Lung Neoplasms/*genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Proteins/*genetics
MH  - Prognosis
MH  - Small Cell Lung Carcinoma/*genetics/pathology
MH  - Tumor Suppressor Protein p53/*genetics
EDAT- 2010/05/07 06:00
MHDA- 2010/11/03 06:00
CRDT- 2010/05/07 06:00
PHST- 2009/04/29 00:00 [received]
PHST- 2010/03/07 00:00 [revised]
PHST- 2010/03/27 00:00 [accepted]
PHST- 2010/05/07 06:00 [entrez]
PHST- 2010/05/07 06:00 [pubmed]
PHST- 2010/11/03 06:00 [medline]
AID - S1877-7821(10)00058-5 [pii]
AID - 10.1016/j.canep.2010.03.018 [doi]
PST - ppublish
SO  - Cancer Epidemiol. 2010 Aug;34(4):472-7. doi: 10.1016/j.canep.2010.03.018. Epub 
      2010 May 4.