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Licensed Unlicensed Requires Authentication Published by De Gruyter May 30, 2019

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

  • Said El Shamieh ORCID logo , Fatima Saleh , Shafka Assaad and Fadi Farhat EMAIL logo


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.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Conflict of interest: The authors declare that there is no conflict of interest regarding the publication of this paper.

  3. Research funding: None declared.

  4. Employment or leadership: None declared.

  5. Honorarium: None declared.

  6. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


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Supplementary Material

The online version of this article offers supplementary material (DOI:

Received: 2018-09-05
Accepted: 2019-03-13
Published Online: 2019-05-30

© 2019 Walter de Gruyter GmbH, Berlin/Boston

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