Diagnostics

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Ovarian/Uterine Cancer Panel

The Ovarian/Uterine Cancer Panel is a comprehensive next-generation sequencing (NGS) panel that analyzes genes associated with increased risks for hereditary ovarian and uterine cancer.

Ovarian cancer affects approximately 1% of women during their lifetime, and uterine cancer affects approximately 2% of women (SEERP). Although the majority of ovarian and uterine cancers are not related to heritable factors, approximately 5% of uterine cancer (Gruber and Thompson, 1996) and at least 10-15% of ovarian cancer are caused by a specific genetic change (Pal et al, 2005). Individuals who carry these genetic changes may be at significantly increased risk of developing ovarian and uterine cancer in their lifetime. The majority of hereditary uterine cancer cases are caused by mutations in the EPCAM, MLH1, MSH2, PMS2, and MSH6 genes, related to Lynch syndrome, while the majority of hereditary ovarian cancer cases are caused by mutations in the BRCA1/2 genes related to hereditary breast and ovarian cancer syndrome (HBOC). Individuals who carry disease causing changes in these genes, and other, rarer genes, are at increased lifetime risks for uterine cancer (up to 60%) and ovarian cancer (up to 63%) (Kohlmann and Gruber, 2004; Petrucelli et al, 1998). Frequently, changes in genes that result in increased risks for uterine and ovarian cancer also predispose individuals to increased risks for other malignancies.

Included Disorders

This panel includes genes associated with:

  • Lynch syndrome (hereditary non-polyposis colon cancer)
  • Hereditary breast and ovarian cancer syndrome (HBOC)
  • Li-Fraumeni syndrome
  • Cowden syndrome
  • Muir-Torre syndrome
  • Sertoli-Leydig cell tumor

Inheritance

Hereditary ovarian and uterine cancers are typically inherited in an autosomal dominant manner, although several of the genes on this panel are associated with recessive genetic conditions:

  • MLH1, MSH2, PMS2, and MSH6 are associated with constitutional mismatch repair deficiency
  • PALB2, RAD51C, and BRCA2 are associated with Fanconi anemia

Indications for Testing

  • A personal history of ovarian cancer
  • A personal history of early uterine cancer
  • A personal history of multiple primary cancers
  • A family history suggestive of a hereditary cancer syndrome, including multiple individuals on the same side of a family diagnosed with cancer, especially at ages below population averages
  • Risk assessment for asymptomatic family of members of proband with molecular diagnosis of a hereditary cancer syndrome

Methodology

Next-generation sequencing technology is used to test clinically relevant portions of each gene, including coding exons, adjacent flanking bases, and selected introns/noncoding variants. Pathogenic and likely pathogenic variants are confirmed by orthogonal methods. Copy number variants, including intragenic deletions and duplications are detected to a resolution of a single exon. To request analysis of a specific single exon copy number variant, please contact our Client Services team prior to ordering.

Included Genes (15)

BRCA1 BRCA2 BRIP1 DICER1 EPCAM MLH1 MSH2 MSH6
PALB2 PMS2 PTEN RAD51C RAD51D SMARCA4 TP53

Additions to the Ovarian/Uterine Cancer Panel:

Emerging evidence genes can also be added onto the comprehensive panel. These genes do not have a clear association with hereditary uterine and ovarian cancer, but emerging evidence suggests that they may play a role in disease pathogenesis.

Emerging Evidence (3):

CHEK2 MUTYH POLD1

References:

  • Gruber SB, Thompson WD. A population-based study of endometrial cancer and familial risk in younger women. Cancer and Steroid Hormone Study Group. Cancer Epidemiol Biomarkers Prev. 1996;5(6):411–417.
  • Kohlmann W, Gruber SB. Lynch Syndrome. 2004 Feb 5 [Updated 2014 May 22]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1211/
  • Pal T, Permuth-Wey J, Betts JA. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer. 2005; 104(12):2807-16.
  • Petrucelli N, Daly MB, Pal T. BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. 1998 Sep 4 [Updated 2016 Dec 15]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1247/
  • Surveillance, Epidemiology, and End Results Program (SEERP). Cancer Stat Fact Sheets [Accessed April 20, 2017]. Available from: http://seer.cancer.gov/