Next-generation sequencing reveals mutations in RB1, CDK4 and TP53 that may promote chemo-resistance to palbociclib in ovarian cancer

Said El Shamieh 1Fatima Saleh 1Shafka Assaad 2Fadi Farhat 3 4

Affiliations

1Department of Medical Laboratory Technology, Faculty of Health Sciences, Beirut Arab University, Beirut, Lebanon.

2Rammal Hassan Rammal Research Laboratory, Physiotoxicity (PhyTox), Faculty of Sciences, Lebanese University, Nabatieh, Lebanon.

3Department of Hematology-Oncology, Saint Joseph Faculty of Medicine, Beirut, Lebanon.

4Department of Hematology and Oncology, Hammoud Hospital UMC, Saida, Lebanon, Phone: +9613753155.

PMID: 31145688

DOI: 10.1515/dmpt-2018-0027

Abstract

Because of the profound heterogeneity of ovarian cancer at the clinical, cellular and molecular levels, herein we discuss the molecular findings at the protein and genetic levels seen in our patient. Immunohistochemistry showed a complete loss of phosphatase and tensin homolog, this observation was the reason behind prescribing the CDK4/6 inhibitor palbociclib. However, there was no response to treatment. Next-generation sequencing analysis was performed showing a nonsense mutation, p.R552X in retinoblastoma 1 (RB1). This nonsense variation will possibly lead to a truncated protein lacking the domain responsible for interaction with E2F, an event that will induce cell cycle progression and, thus, be responsible for the chemo-resistance to palbociclib.

Keywords: mutations; next-generation sequencing; ovarian cancer; personalized therapy.