TY - JOUR
T1 - Genome-wide analysis of loss of heterozygosity and copy number amplification in uterine leiomyomas using the 100K single nucleotide polymorphism array
AU - Meadows, Kellen L.
AU - Andrews, Danica M.K.
AU - Xu, Zongli
AU - Carswell, Gleta K.
AU - Laughlin, Shannon K.
AU - Baird, Donna D.
AU - Taylor, Jack A.
N1 - Funding Information:
This research was supported by the Intramural Research Program of the NIH , National Institute of Environmental Health Sciences. Financial support for the parent study, The Fibroid Growth Study, was provided by NIEHS, NIH intramural funding and the National Center for Research on Minority Health and Health Disparities, NIH. Barbara Davis and Shyamal Peddada provided design and oversight of the parent study. Ania Kowalik was the clinical leader of the field study. Karen Haneke and Heather Vahdat managed the field study and the study data. Martha Turvey was the study nurse, Xiaoyu Ding conducted the pathological analyses of tumor tissue, and Pamela Blackshear aided in tissue analyses. Anne Marie Jukic and Lisa Chadwick provided comments on the manuscript.
PY - 2011/8
Y1 - 2011/8
N2 - Purpose: Uterine leiomyomas (fibroids) are benign smooth muscle tumors commonly found among reproductive-aged women. Though benign, these tumors are the leading indication for hysterectomies in the United States and cause significant morbidity. Despite the importance of this tumor in women's health, relatively little is known about the molecular etiology. Methods: In this study, we used the Affymetrix 100K single nucleotide polymorphism (SNP) chip to assess whether the pattern and frequency of genome-wide loss of heterozygosity (LOH) and copy number amplifications is associated with clinical heterogeneity. Results: Thirty-seven tumors with varying sizes and histology from eleven patients were analyzed. LOH was observed in 4/37 tumors (10.8%) and significantly associated with large-sized tumors (p < 0.0014). Two tumors revealed hemizygosity on chromosome 7q, a region that has been consistently reported to have LOH. Additionally, we detected one novel region of LOH, 16p13.11 in one tumor (2.7%). Copy number amplifications were observed on all chromosomes; however, most were low-level amplifications and only detected in a single tumor. One region of amplification at 3p26.3 was detected in four tumors. Conclusions: Despite the use of a high-density SNP platform, our results suggest that genome-wide LOH and copy number amplifications are infrequent events and generally do not determine clinical and histologic characteristics of this disease.
AB - Purpose: Uterine leiomyomas (fibroids) are benign smooth muscle tumors commonly found among reproductive-aged women. Though benign, these tumors are the leading indication for hysterectomies in the United States and cause significant morbidity. Despite the importance of this tumor in women's health, relatively little is known about the molecular etiology. Methods: In this study, we used the Affymetrix 100K single nucleotide polymorphism (SNP) chip to assess whether the pattern and frequency of genome-wide loss of heterozygosity (LOH) and copy number amplifications is associated with clinical heterogeneity. Results: Thirty-seven tumors with varying sizes and histology from eleven patients were analyzed. LOH was observed in 4/37 tumors (10.8%) and significantly associated with large-sized tumors (p < 0.0014). Two tumors revealed hemizygosity on chromosome 7q, a region that has been consistently reported to have LOH. Additionally, we detected one novel region of LOH, 16p13.11 in one tumor (2.7%). Copy number amplifications were observed on all chromosomes; however, most were low-level amplifications and only detected in a single tumor. One region of amplification at 3p26.3 was detected in four tumors. Conclusions: Despite the use of a high-density SNP platform, our results suggest that genome-wide LOH and copy number amplifications are infrequent events and generally do not determine clinical and histologic characteristics of this disease.
KW - Copy number amplification
KW - LOH
KW - Single nucleotide polymorphism array
KW - Uterine leiomyoma
UR - http://www.scopus.com/inward/record.url?scp=79956218087&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79956218087&partnerID=8YFLogxK
U2 - 10.1016/j.yexmp.2011.03.007
DO - 10.1016/j.yexmp.2011.03.007
M3 - Article
C2 - 21497600
AN - SCOPUS:79956218087
SN - 0014-4800
VL - 91
SP - 434
EP - 439
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
IS - 1
ER -