PMID- 20800559
OWN - NLM
STAT- MEDLINE
DCOM- 20110531
LR  - 20240326
IS  - 1878-0261 (Electronic)
IS  - 1574-7891 (Print)
IS  - 1574-7891 (Linking)
VI  - 5
IP  - 1
DP  - 2011 Feb
TI  - Genomic instability and copy-number heterogeneity of chromosome 19q, including 
      the kallikrein locus, in ovarian carcinomas.
PG  - 48-60
LID - 10.1016/j.molonc.2010.08.002 [doi]
AB  - Many tissue kallikrein (KLK) genes and proteins are candidate diagnostic, 
      prognostic and predictive biomarkers for ovarian cancer (OCa). We previously 
      demonstrated that the KLK locus (19q13.3/4) is subject to copy-number gains and 
      structural rearrangements in a pilot study of cell lines and ovarian cancer 
      primary tissues, shown to overexpress KLK gene family members. To determine the 
      overall frequency of genomic instability and copy-number changes, a retrospective 
      study was conducted using formalin-fixed paraffin embedded (FFPE) tissues. 
      Eighty-one chemotherapy naive serous OCas were examined using 3-colour 
      fluorescence in situ hybridization (FISH) to identify structural and numerical 
      changes on 19q, including the KLK locus; in addition to immunohistochemistry 
      (IHC) for KLK6, which has been shown to be overexpressed in OCa. The KLK locus 
      was subject to copy-number changes in  approximately 83% of cases: net gain in 51%, net loss in 
      30% and amplified in 2%; and found to be chromosomally unstable (p < 0.001). All 
      cases showed a wide range of immuoreactivity for KLK6 by IHC. Although no strong 
      correlation could be found with copy-number, the latter was contributing factor 
      to the observed KLK6 protein overexpression. Moreover, univariate and 
      multivariate analyses showed an association between the net loss of the KLK locus 
      and longer disease-free survival. Interestingly, FISH analyses indicated that 
      chromosome 19q was subjected to structural rearrangement in 62% of cases and was 
      significantly correlated to tumor grade (p < 0.001). We conclude that numerical 
      and structural aberrations of chromosome 19q, affect genes including the KLK gene 
      members, may contribute to ovarian carcinoma progression and aggressiveness.
CI  - Copyright (c) 2010 Federation of European Biochemical Societies. Published by 
      Elsevier B.V. All rights reserved.
FAU - Bayani, Jane
AU  - Bayani J
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Toronto, Ontario, Canada. jane.bayani@utoronto.ca
FAU - Marrano, Paula
AU  - Marrano P
FAU - Graham, Cassandra
AU  - Graham C
FAU - Zheng, Yingye
AU  - Zheng Y
FAU - Li, Lin
AU  - Li L
FAU - Katsaros, Dionyssios
AU  - Katsaros D
FAU - Lassus, Heini
AU  - Lassus H
FAU - Butzow, Ralf
AU  - Butzow R
FAU - Squire, Jeremy A
AU  - Squire JA
FAU - Diamandis, Eleftherios P
AU  - Diamandis EP
LA  - eng
GR  - R01 CA120197/CA/NCI NIH HHS/United States
GR  - R01 CA120197-01/CA/NCI NIH HHS/United States
GR  - R01 CA120197-02/CA/NCI NIH HHS/United States
GR  - R01 CA120197-03/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100811
PL  - United States
TA  - Mol Oncol
JT  - Molecular oncology
JID - 101308230
RN  - EC 3.4.21.- (Kallikreins)
SB  - IM
MH  - *Chromosomes, Human, Pair 19
MH  - Female
MH  - *Gene Dosage
MH  - *Genetic Heterogeneity
MH  - *Genomic Instability
MH  - Humans
MH  - Immunohistochemistry
MH  - Kallikreins/*genetics
MH  - Ovarian Neoplasms/*genetics
PMC - PMC3110681
MID - NIHMS289073
EDAT- 2010/08/31 06:00
MHDA- 2011/06/01 06:00
PMCR- 2011/02/01
CRDT- 2010/08/31 06:00
PHST- 2010/07/07 00:00 [received]
PHST- 2010/08/03 00:00 [revised]
PHST- 2010/08/04 00:00 [accepted]
PHST- 2010/08/31 06:00 [entrez]
PHST- 2010/08/31 06:00 [pubmed]
PHST- 2011/06/01 06:00 [medline]
PHST- 2011/02/01 00:00 [pmc-release]
AID - S1574-7891(10)00083-9 [pii]
AID - MOL220115148 [pii]
AID - 10.1016/j.molonc.2010.08.002 [doi]
PST - ppublish
SO  - Mol Oncol. 2011 Feb;5(1):48-60. doi: 10.1016/j.molonc.2010.08.002. Epub 2010 Aug 
      11.