Exome Sequencing of Ovarian Cancer Patients to Identify Variants Predictive of Sensitivity to Platinum-based Chemotherapy

Title:Exome Sequencing of Ovarian Cancer Patients to Identify Variants Predictive of Sensitivity to Platinum-based Chemotherapy

Volume: 14 Issue: 2

Author(s): Assaad Y. Semaan, Kristin R. Delfino, Andrew C. Wilber, Thomas K. Mathews, Kathy J. Robinson, Laurent Brard and Shaheen R. Alanee*

Affiliation:

• Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI,United States

Keywords: Chemotherapy, exome, sensitivity, sequencing, single nucleotide polymorphism, ovarian cancer.

Abstract: Background: By using exome sequencing, we envisioned that certain single nucleotide variants (SNVs), predictive of sensitivity to platinum treatment, could be discovered.

Methods: Twenty-two Platinum-Sensitive (Pt-S) and 6 Platinum-Resistant (Pt-R) ovarian cancer patients were tested. Platinum sensitivity was defined as disease free survival greater than 6 months. Next-generation sequencing of exomes was used to compare Pt-S and Pt-R patients. SNVs associated with platinum sensitivity were identified using Ingenuity Variant Analysis.

Results: No SNV was significantly associated with sensitivity to platinum treatment after correcting for multiple comparison, however, three genes included a significantly higher number of SNVs previously shown to have pharmacogenetics associations (pSNV) in Pt-S patients when compared to Pt-R patients. Insulin-like growth factor 1 receptor (IGF1R) contained pSNVs in 59% of Pt-S and 0% of Pt-R (14 variants, p=1.25 E-2). Liproteinrelated protein 2 (LRP2) contained pSNVs in 54% of Pt-S and 0% of Pt-R (12 variants, p=3.20 E-2), and non-SMC condensin I complex subunit D2 (NCAPD2) contained pSNVs in 50% of Pt-S and 0% of Pt-R (7 variants, p=4.71 E-2). Three genes included a significantly higher number of pSNVs in Pt-R when compared to Pt-S patients. AF4/FMR2 family member 1 (AFF1) contained pSNVs in 50% of Pt-R and 0% of Pt-S (3 variants, p=3.20 E-3), breast cancer type 2 susceptibility protein (BRCA2) contained pSNVs in 50% Pt-R and 0% of Pt-S (3 variants, p=2.40 E-3), and DNA-dependent protein kinase (PRKDC) contained pSNVs in 50% of Pt-R and 0% of Pt-S (3 variants, p=2.90 E-3).

Conclusion: pSNVs load in certain genes may be predictive of sensitivity to platinum in ovarian cancer. With validation of these findings, it is possible that a new marker predictive of patient response may be identified.

Cite this article as:

Semaan Y. Assaad, Delfino R. Kristin, Wilber C. Andrew, Mathews K. Thomas, Robinson J. Kathy, Brard Laurent and Alanee R. Shaheen*, Exome Sequencing of Ovarian Cancer Patients to Identify Variants Predictive of Sensitivity to Platinum-based Chemotherapy, Current Pharmacogenomics and Personalized Medicine 2016; 14 (2) . https://dx.doi.org/10.2174/1875692115666170126152349

DOI https://dx.doi.org/10.2174/1875692115666170126152349	Print ISSN 1875-6921
Publisher Name Bentham Science Publisher	Online ISSN 1875-6913