Genome-wide Analysis of Loss of Heterozygosity and Copy Number Amplification in Uterine Leiomyomas Using the 100K Single Nucleotide Polymorphism Array

Overview

Journal Exp Mol Pathol

Publisher Elsevier

Specialties Molecular Biology
Pathology

Date 2011 Apr 19

PMID 21497600

Citations 2

Authors

Kellen L Meadows

Danica M K Andrews

Zongli Xu

Gleta K Carswell

Shannon K Laughlin

Donna D Baird

Jack A Taylor

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Cytogenomic Profile of Uterine Leiomyoma: In Vivo vs. In Vitro Comparison.

Koltsova A, Efimova O, Malysheva O, Osinovskaya N, Liehr T, Al-Rikabi A Biomedicines. 2021; 9(12).

PMID: 34944592 PMC: 8698342. DOI: 10.3390/biomedicines9121777.

Uterine smooth muscle tumor analysis by comparative genomic hybridization: a useful diagnostic tool in challenging lesions.

Croce S, Ribeiro A, Brulard C, Noel J, Amant F, Stoeckle E Mod Pathol. 2015; 28(7):1001-10.

PMID: 25932961 DOI: 10.1038/modpathol.2015.3.

References

Lee D, Ozminkowski R, Carls G, Wang S, Gibson T, Stewart E . The direct and indirect cost burden of clinically significant and symptomatic uterine fibroids. J Occup Environ Med. 2007; 49(5):493-506. DOI: 10.1097/JOM.0b013e31805f6cf2. View

Levy B, Mukherjee T, Hirschhorn K . Molecular cytogenetic analysis of uterine leiomyoma and leiomyosarcoma by comparative genomic hybridization. Cancer Genet Cytogenet. 2000; 121(1):1-8. DOI: 10.1016/s0165-4608(00)00225-9. View

Beroukhim R, Lin M, Park Y, Hao K, Zhao X, Garraway L . Inferring loss-of-heterozygosity from unpaired tumors using high-density oligonucleotide SNP arrays. PLoS Comput Biol. 2006; 2(5):e41. PMC: 1458964. DOI: 10.1371/journal.pcbi.0020041. View

Kataoka S, Yamada H, Hoshi N, Kudo M, Hareyama H, Sakuragi N . Cytogenetic analysis of uterine leiomyoma: the size, histopathology and GnRHa-response in relation to chromosome karyotype. Eur J Obstet Gynecol Reprod Biol. 2003; 110(1):58-62. DOI: 10.1016/s0301-2115(03)00075-7. View

Davis B, Haneke K, Miner K, Kowalik A, Barrett J, Peddada S . The fibroid growth study: determinants of therapeutic intervention. J Womens Health (Larchmt). 2009; 18(5):725-32. PMC: 2851130. DOI: 10.1089/jwh.2008.0903. View

Hartmann K, Birnbaum H, Ben-Hamadi R, Wu E, Farrell M, Spalding J . Annual costs associated with diagnosis of uterine leiomyomata. Obstet Gynecol. 2006; 108(4):930-7. DOI: 10.1097/01.AOG.0000234651.41000.58. View

Lieberfarb M, Lin M, Lechpammer M, Li C, Tanenbaum D, Febbo P . Genome-wide loss of heterozygosity analysis from laser capture microdissected prostate cancer using single nucleotide polymorphic allele (SNP) arrays and a novel bioinformatics platform dChipSNP. Cancer Res. 2003; 63(16):4781-5. View

Ligon A, Morton C . Genetics of uterine leiomyomata. Genes Chromosomes Cancer. 2000; 28(3):235-45. View

Hennig Y, Deichert U, Bonk U, Thode B, Bartnitzke S, Bullerdiek J . Chromosomal translocations affecting 12q14-15 but not deletions of the long arm of chromosome 7 associated with a growth advantage of uterine smooth muscle cells. Mol Hum Reprod. 1999; 5(12):1150-4. DOI: 10.1093/molehr/5.12.1150. View

10.

Baird D, Dunson D, Hill M, Cousins D, Schectman J . High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol. 2003; 188(1):100-7. DOI: 10.1067/mob.2003.99. View

11.

Flake G, Andersen J, Dixon D . Etiology and pathogenesis of uterine leiomyomas: a review. Environ Health Perspect. 2003; 111(8):1037-54. PMC: 1241553. DOI: 10.1289/ehp.5787. View

12.

Packenham J, Du Manoir S, Schrock E, Risinger J, Dixon D, Denz D . Analysis of genetic alterations in uterine leiomyomas and leiomyosarcomas by comparative genomic hybridization. Mol Carcinog. 1997; 19(4):273-9. DOI: 10.1002/(sici)1098-2744(199708)19:4<273::aid-mc9>3.0.co;2-d. View

13.

de Azevedo Canevari R, Pontes A, Rogatto S . Microallelotyping defines novel regions of loss of heterozygosity in uterine leiomyomas. Mol Carcinog. 2004; 42(3):177-82. DOI: 10.1002/mc.20074. View

14.

Zhao X, Li C, Paez J, Chin K, Janne P, Chen T . An integrated view of copy number and allelic alterations in the cancer genome using single nucleotide polymorphism arrays. Cancer Res. 2004; 64(9):3060-71. DOI: 10.1158/0008-5472.can-03-3308. View

15.

Huang J, Wei W, Zhang J, Liu G, Bignell G, Stratton M . Whole genome DNA copy number changes identified by high density oligonucleotide arrays. Hum Genomics. 2004; 1(4):287-99. PMC: 3525261. DOI: 10.1186/1479-7364-1-4-287. View

16.

Vanharanta S, Wortham N, Laiho P, Sjoberg J, Aittomaki K, Arola J . 7q deletion mapping and expression profiling in uterine fibroids. Oncogene. 2005; 24(43):6545-54. DOI: 10.1038/sj.onc.1208784. View

17.

Stewart E . Uterine fibroids. Lancet. 2001; 357(9252):293-8. DOI: 10.1016/S0140-6736(00)03622-9. View

18.

Lindblad-Toh K, Tanenbaum D, Daly M, Winchester E, Lui W, Villapakkam A . Loss-of-heterozygosity analysis of small-cell lung carcinomas using single-nucleotide polymorphism arrays. Nat Biotechnol. 2000; 18(9):1001-5. DOI: 10.1038/79269. View

19.

Lengauer C, Kinzler K, Vogelstein B . Genetic instabilities in human cancers. Nature. 1999; 396(6712):643-9. DOI: 10.1038/25292. View

20.

Di X, Matsuzaki H, Webster T, Hubbell E, Liu G, Dong S . Dynamic model based algorithms for screening and genotyping over 100 K SNPs on oligonucleotide microarrays. Bioinformatics. 2005; 21(9):1958-63. DOI: 10.1093/bioinformatics/bti275. View