Characterization of the common fragile site FRA9E and its potential role in ovarian cancer

Gwen Callahan; Stacy R. Denison; Leslie A. Phillips; Viji Shridhar; David I. Smith

doi:10.1038/sj.onc.1206171

Characterization of the common fragile site FRA9E and its potential role in ovarian cancer

Gwen Callahan, Stacy R. Denison, Leslie A. Phillips, Viji Shridhar, David I. Smith

Research output: Contribution to journal › Article › peer-review

63 Scopus citations

Abstract

Common fragile sites (CFSs) are regions of profound genomic instability that have been hypothesized to play a role in cancer. The major aim of this study was to locate a fragile region associated with ovarian cancer. Differential display (DD)-PCR analysis comparing normal ovarian epithelial cultures and ovarian cancer cell lines identified pregnancy-associated plasma protein-A (PAPPA) because of its frequent loss of expression (LOE) in ovarian cancer cell lines. PAPPA is localized to human chromosome 9q32-33.1, a region associated with significant loss of heterozygosity (LOH) in ovarian tumors (> 50%) and in close proximity to the FRA9E CFS. FISH analysis determined that PAPPA was contained within the distal end of FRA9E. Characterization of FRA9E determined that aphidicolin-induced instability extended over 9Mb, identifying FRA9E as the largest CFS characterized to date. Comprehensive LOH analysis revealed several distinct peaks of LOH within FRA9E. Semiquantitative RT-PCR analysis of 16 genes contained within FRA9E indicated that genes showing LOE in ovarian tumors coincided with regions of high LOH. PAPPA displayed the most significant loss (72%). This study provides evidence to suggest that instability within FRA9E may play an important role in the development of ovarian cancer and lends further support for the hypothesis that CFSs may be causally related to cancer.

Original language	English (US)
Pages (from-to)	590-601
Number of pages	12
Journal	Oncogene
Volume	22
Issue number	4
DOIs	https://doi.org/10.1038/sj.onc.1206171
State	Published - Jan 30 2003

Keywords

Chromosomal deletions
Common fragile sites
FRA9E
Ovarian cancer
PAPPA

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

Access to Document

10.1038/sj.onc.1206171

Cite this

@article{58ae33c937ad442a8198cf05609d22f9,

title = "Characterization of the common fragile site FRA9E and its potential role in ovarian cancer",

abstract = "Common fragile sites (CFSs) are regions of profound genomic instability that have been hypothesized to play a role in cancer. The major aim of this study was to locate a fragile region associated with ovarian cancer. Differential display (DD)-PCR analysis comparing normal ovarian epithelial cultures and ovarian cancer cell lines identified pregnancy-associated plasma protein-A (PAPPA) because of its frequent loss of expression (LOE) in ovarian cancer cell lines. PAPPA is localized to human chromosome 9q32-33.1, a region associated with significant loss of heterozygosity (LOH) in ovarian tumors (> 50%) and in close proximity to the FRA9E CFS. FISH analysis determined that PAPPA was contained within the distal end of FRA9E. Characterization of FRA9E determined that aphidicolin-induced instability extended over 9Mb, identifying FRA9E as the largest CFS characterized to date. Comprehensive LOH analysis revealed several distinct peaks of LOH within FRA9E. Semiquantitative RT-PCR analysis of 16 genes contained within FRA9E indicated that genes showing LOE in ovarian tumors coincided with regions of high LOH. PAPPA displayed the most significant loss (72%). This study provides evidence to suggest that instability within FRA9E may play an important role in the development of ovarian cancer and lends further support for the hypothesis that CFSs may be causally related to cancer.",

keywords = "Chromosomal deletions, Common fragile sites, FRA9E, Ovarian cancer, PAPPA",

author = "Gwen Callahan and Denison, {Stacy R.} and Phillips, {Leslie A.} and Viji Shridhar and Smith, {David I.}",

note = "Funding Information: We thank Dr Kimberly Kalli and Kimberly Stephens for providing the short-term normal ovarian epithelial (OSE) cultures. This study was conducted as a component of GC{\textquoteright}s doctoral thesis requirements in the Mayo Graduate School. GC{\textquoteright}s training has been supported, in part, by an NIH training Grant (CA 75926) to the Tumor Biology Program of the Mayo Graduate School and by the Mayo Clinic Foundation. This work was supported by NCI Grant CA48031 and DOD Grant DAMD17-99-1-9504 (both to DIS).",

year = "2003",

month = jan,

day = "30",

doi = "10.1038/sj.onc.1206171",

language = "English (US)",

volume = "22",

pages = "590--601",

journal = "Oncogene",

issn = "0950-9232",

publisher = "Nature Publishing Group",

number = "4",

}

TY - JOUR

T1 - Characterization of the common fragile site FRA9E and its potential role in ovarian cancer

AU - Callahan, Gwen

AU - Denison, Stacy R.

AU - Phillips, Leslie A.

AU - Shridhar, Viji

AU - Smith, David I.

N1 - Funding Information: We thank Dr Kimberly Kalli and Kimberly Stephens for providing the short-term normal ovarian epithelial (OSE) cultures. This study was conducted as a component of GC’s doctoral thesis requirements in the Mayo Graduate School. GC’s training has been supported, in part, by an NIH training Grant (CA 75926) to the Tumor Biology Program of the Mayo Graduate School and by the Mayo Clinic Foundation. This work was supported by NCI Grant CA48031 and DOD Grant DAMD17-99-1-9504 (both to DIS).

PY - 2003/1/30

Y1 - 2003/1/30

N2 - Common fragile sites (CFSs) are regions of profound genomic instability that have been hypothesized to play a role in cancer. The major aim of this study was to locate a fragile region associated with ovarian cancer. Differential display (DD)-PCR analysis comparing normal ovarian epithelial cultures and ovarian cancer cell lines identified pregnancy-associated plasma protein-A (PAPPA) because of its frequent loss of expression (LOE) in ovarian cancer cell lines. PAPPA is localized to human chromosome 9q32-33.1, a region associated with significant loss of heterozygosity (LOH) in ovarian tumors (> 50%) and in close proximity to the FRA9E CFS. FISH analysis determined that PAPPA was contained within the distal end of FRA9E. Characterization of FRA9E determined that aphidicolin-induced instability extended over 9Mb, identifying FRA9E as the largest CFS characterized to date. Comprehensive LOH analysis revealed several distinct peaks of LOH within FRA9E. Semiquantitative RT-PCR analysis of 16 genes contained within FRA9E indicated that genes showing LOE in ovarian tumors coincided with regions of high LOH. PAPPA displayed the most significant loss (72%). This study provides evidence to suggest that instability within FRA9E may play an important role in the development of ovarian cancer and lends further support for the hypothesis that CFSs may be causally related to cancer.

AB - Common fragile sites (CFSs) are regions of profound genomic instability that have been hypothesized to play a role in cancer. The major aim of this study was to locate a fragile region associated with ovarian cancer. Differential display (DD)-PCR analysis comparing normal ovarian epithelial cultures and ovarian cancer cell lines identified pregnancy-associated plasma protein-A (PAPPA) because of its frequent loss of expression (LOE) in ovarian cancer cell lines. PAPPA is localized to human chromosome 9q32-33.1, a region associated with significant loss of heterozygosity (LOH) in ovarian tumors (> 50%) and in close proximity to the FRA9E CFS. FISH analysis determined that PAPPA was contained within the distal end of FRA9E. Characterization of FRA9E determined that aphidicolin-induced instability extended over 9Mb, identifying FRA9E as the largest CFS characterized to date. Comprehensive LOH analysis revealed several distinct peaks of LOH within FRA9E. Semiquantitative RT-PCR analysis of 16 genes contained within FRA9E indicated that genes showing LOE in ovarian tumors coincided with regions of high LOH. PAPPA displayed the most significant loss (72%). This study provides evidence to suggest that instability within FRA9E may play an important role in the development of ovarian cancer and lends further support for the hypothesis that CFSs may be causally related to cancer.

KW - Chromosomal deletions

KW - Common fragile sites

KW - FRA9E

KW - Ovarian cancer

KW - PAPPA

UR - http://www.scopus.com/inward/record.url?scp=0037473048&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037473048&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1206171

DO - 10.1038/sj.onc.1206171

M3 - Article

C2 - 12555072

AN - SCOPUS:0037473048

SN - 0950-9232

VL - 22

SP - 590

EP - 601

JO - Oncogene

JF - Oncogene

IS - 4

ER -

Characterization of the common fragile site FRA9E and its potential role in ovarian cancer

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this