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Tumor Molecular Testing > For Ovarian Cancer

 

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Personalized Treatment Designed For Cancer Patients

Ovarian Cancer Panel

Epithelial ovarian cancer (EOC) is the most common cause of gynecological cancer death in the United States, with a  vast majority of women are diagnosed with advanced stage EOC. Current practice consists of aggressive surgical removal of tumors, followed by platinum–taxane based chemotherapy (Muggia 2009). Despite initial aggressive treatment, most tumors recur, and the overall 5-year survival rate is 44% (Siegel, Naishadham, and Jemal 2012).

Emerging knowledge about underlying molecular alterations in ovarian cancer could allow for more personalized diagnostic, predictive, prognostic, and therapeutic strategies. Approximately 10–20% of high grade ovarian cancers are associated with germline mutations in BRCA1/2 (Pal et al. 2005). Somatic alterations in BRCA1/2 and other genes associated with DNA repair are seen in approximately 50% of high grade ovarian cancers (TCGA 2011) and tumors with a ‘BRCAness’ molecular profile are relatively sensitive to treatment with DNA damaging agents cisplatin and PARP inhibitors (Konstantinopoulos et al. 2010).
 More recently, EOC tumors have been broadly classified into two distinct groups with unique histological, clinical and molecular profiles (Table 1). Type I tumors have low grade serous, clear cell, endometrioid, and mucinous histological features. Typically, these tumors are slow growing and confined to the ovary, and are less sensitive to standard chemotherapy. BRAF and KRAS somatic mutations are relatively common in these tumors, which may have important therapeutic implications.

Type II tumors are high grade serous cancers of the ovary, peritoneum, and fallopian tube. Other high grade endometrioid and poorly differentiated ovarian cancers as well as carcinosarcomas are included in the type II group. These tumors are clinically aggressive and are often widely metastatic at the time of presentation. High grade serous EOC tumors display high levels of genomic instability with few common mutations, other than TP53, which is altered in over 90% of the cases (Kurman and Shih 2011; Landen, Birrer, and Sood 2008; TCGA 2011). PIK3CA and RAS signaling pathways are altered in 45% of the cases, but somatic mutations are rare and gene amplifications are far more common (TCGA 2011).​Currently, the most common ‘actionable’ alterations with potential for small molecule targeted therapy in EOC tumors are in the PIK3CA/PTEN and KRAS/BRAF signaling pathways.

Genes and Their Locations

6q25.1

ER
TLE3

15q23

TOPO1

20q12

RRM1

11p15.4

TS

15q14

SPARC

5q33.1

CMET

7q31.2

TOP2A

17q21.2

BRAF

7q34

PTEN

10q23.3

PGP

16p13.3

BRCA1

17q21.31

ERCC1

19q13.32

PIK3CA

3q26.32

KRAS

12p12.1