Presentation Title

Loss of CDKN1C in a Recurrent Atypical Teratoid/Rhabdoid Tumor

Speaker Credentials

OMS-I

College

Dr. Kiran C. Patel College of Osteopathic Medicine, DO

Location

Nova Southeastern University, Davie, Florida, USA

Format

Poster

Start Date

16-2-2018 12:15 PM

End Date

16-2-2018 1:15 PM

Abstract

Introduction. We present the case of a child with recurrent atypical teratoid/rhabdoid tumor (AT/RT) who underwent clinically integrated molecular sequencing that revealed a novel loss-of-function mutation in CDKN1C alongside hallmark loss of SMARCB1. Case Presentation. A 6-week-old African-American female presented with respiratory distress, irritability, lethargy, and bulging fontanelle. MRI revealed a right posterior fossa mass with obstructive hydrocephalus. 8 months after gross tumor resection she returned with a recurrent right frontal lobe lesion and underwent palliative subtotal resection. Deviation From the Expected. In addition to biallelic loss of SMARCB1, a mutation in CDKN1C was reported and confirmed by immunohistochemistry and whole-exome and transcriptome sequencing in AT/RT. Discussion. Alisertib, an Aurora Kinase A (AURKA) inhibitor, was chosen for our patient due to previously published efficacy of the single-agent therapy in patients with recurrent AT/RT. Conclusion. Sequencing of the recurrent AT/RT revealed a novel mutation in CDKN1C could provide AT/RT new pathways for growth in addition to loss of AURKA regulation. Literature review strengthens evidence of a central upstream regulator, LIN28B, for both CDKN1C and AURKA. Further clarification of this oncogenic pathway in AT/RT should enable the development of improved targeted therapies in this patient population and provide perspective for future cancer research and therapies. Grants. The University of Michigan PEDS-MIONCOSEQ study was supported by grant 1UM1HG006508 from the National Institutes of Health Clinical Sequencing Exploratory Research Award (PI: Arul Chinnaiyan, Co-I: Rajen Mody). Carl Koschmann is supported by NIH/NINDS grant K08-NS099427-01.

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Feb 16th, 12:15 PM Feb 16th, 1:15 PM

Loss of CDKN1C in a Recurrent Atypical Teratoid/Rhabdoid Tumor

Nova Southeastern University, Davie, Florida, USA

Introduction. We present the case of a child with recurrent atypical teratoid/rhabdoid tumor (AT/RT) who underwent clinically integrated molecular sequencing that revealed a novel loss-of-function mutation in CDKN1C alongside hallmark loss of SMARCB1. Case Presentation. A 6-week-old African-American female presented with respiratory distress, irritability, lethargy, and bulging fontanelle. MRI revealed a right posterior fossa mass with obstructive hydrocephalus. 8 months after gross tumor resection she returned with a recurrent right frontal lobe lesion and underwent palliative subtotal resection. Deviation From the Expected. In addition to biallelic loss of SMARCB1, a mutation in CDKN1C was reported and confirmed by immunohistochemistry and whole-exome and transcriptome sequencing in AT/RT. Discussion. Alisertib, an Aurora Kinase A (AURKA) inhibitor, was chosen for our patient due to previously published efficacy of the single-agent therapy in patients with recurrent AT/RT. Conclusion. Sequencing of the recurrent AT/RT revealed a novel mutation in CDKN1C could provide AT/RT new pathways for growth in addition to loss of AURKA regulation. Literature review strengthens evidence of a central upstream regulator, LIN28B, for both CDKN1C and AURKA. Further clarification of this oncogenic pathway in AT/RT should enable the development of improved targeted therapies in this patient population and provide perspective for future cancer research and therapies. Grants. The University of Michigan PEDS-MIONCOSEQ study was supported by grant 1UM1HG006508 from the National Institutes of Health Clinical Sequencing Exploratory Research Award (PI: Arul Chinnaiyan, Co-I: Rajen Mody). Carl Koschmann is supported by NIH/NINDS grant K08-NS099427-01.