Childhood Cancer Data Initiative Annual Symposium (Abstract Registration): Submission #53

Submission information

Submission Number: 53

Submission ID: 150418

Submission UUID: 0497f474-cdd5-4281-9c88-a4e47fd4229b

Submission URI: /nci/ccdisymposium/abstract

Submission Update: /nci/ccdisymposium/abstract?token=XhdPLNcYYC8rRuXy9K55nG_gWBBWjbsqwg9Py8vLC9g

Created: Fri, 08/29/2025 - 17:50

Completed: Fri, 08/29/2025 - 18:02

Changed: Fri, 08/29/2025 - 18:02

Remote IP address: 10.208.28.51

Submitted by: Anonymous

Language: English

Is draft: No

Webform: Childhood Cancer Data Initiative Annual Symposium (Abstracts Submission)

Submitted to: Childhood Cancer Data Initiative Annual Symposium (Abstract Registration)

Abstract Title:	Neuroblastoma Patient-Derived Xenografts and Cell Lines from Postmortem Blood as Models to Understand and Reverse Therapy Resistance
Abstract:	Patient-derived models of neuroblastoma are essential for defining resistance mechanisms and for preclinical studies seeking to reverse drug resistance. We have established and characterized patient derived xenografts (PDXs) and patient derived cell lines (PDCLs) from neuroblastoma patients with progressive disease from samples obtained post-mortem (PD-PM).Tumor and blood samples were cultured and/or subcutaneously xenografted into NOD SCIDγ mice. PDCLs and PDXs were validated by STR profiling and confirmed to be free of Epstein–Barr virus and mycoplasma. Whole exome sequencing identified mutations; telomere maintenance mechanisms were assessed using TERT qPCR, C-circle assay, and TERT break-apart FISH. Therapeutic responses were evaluated in subcutaneous xenografts. PD-PM specimens showed higher xenograft engraftment rates (68%; 21 of 31 specimens, 83% for PD-PM blood specimens) and higher PDCL take rates (54%, 25 of 46 specimens) compared to diagnosis (Dx, 17%) or progressive disease (PD, 11%, P<0.001) specimens. PD-PM PDXs exhibited higher mutation burdens than Dx PDXs (P=0.026), with 33% harboring canonical activating ALK mutations and another 33% having mutations in other RAS-MAPK signaling genes. Among 20 high TERT-expressing PD-PM PDXs, 13 had MYCN amplification; 4 MYCN non-amplified PDXs exhibited TERT rearrangements. One PD-PM PDX was alternative lengthening of telomeres positive. Relative to one Dx and one PD PDXs, duration of response to temozolomide + irinotecan was low in 3 PD-PM PDXs (P<0.001). Thus, PD-PM PDXs activate ALK or RAS-MAPK signaling, manifest high levels of therapy resistance, and provide models to study reversing drug resistance. These PDXs are freely available from the COG/ALSF Childhood Cancer Repository (https://cccells.org).
Abstract:
Authors:	First Name: Balakrishna Last Name: Koneru Degree(s): PhD Organization: Texas Tech University Health Sciences Center School of Medicine Lubbock, TX, USA First Name: Nighat Last Name: Noureen Degree(s): PhD Organization: Texas Tech University Health Sciences Center School of Medicine Lubbock, TX, USA First Name: Ashly Last Name: Hindle Degree(s): PhD Organization: Texas Tech University Health Sciences Center School of Medicine Lubbock, TX, USA First Name: Kristyn Last Name: McCoy Degree(s): MS Organization: Texas Tech University Health Sciences Center School of Medicine Lubbock, TX, USA First Name: Jonas Last Name: Nance Degree(s): BS Organization: Texas Tech University Health Sciences Center School of Medicine Lubbock, TX, USA First Name: Diana Last Name: Ixlamati-Nava Degree(s): BS Organization: Texas Tech University Health Sciences Center School of Medicine Lubbock, TX, USA First Name: Mohamad Last Name: Al-Rahwan Degree(s): MD Organization: Texas Tech University Health Sciences Center School of Medicine Lubbock, TX, USA First Name: Yael Middle Initial: P Last Name: Mosse Degree(s): MD Organization: Division of Oncology and Center for Childhood Cancer Research; Children’s Hospital of Philadelphia, Philadelphia, PA USA First Name: John Middle Initial: M Last Name: Maris Degree(s): MD Organization: Division of Oncology and Center for Childhood Cancer Research; Children’s Hospital of Philadelphia, Philadelphia, PA USA First Name: Shahab Last Name: Asgharzadeh Degree(s): MD Organization: Children's Hospital of Los Angeles, Los Angeles, CA, USA First Name: Araz Last Name: Marachelian Degree(s): MD Organization: Children's Hospital of Los Angeles, Los Angeles, CA, USA First Name: Meredith Middle Initial: S Last Name: Irwin Degree(s): MD Organization: Department of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, Canada First Name: Suzanne Last Name: Shusterman Degree(s): MD Organization: Dana-Farber/Harvard Cancer Center, Boston, MA, USA First Name: Stephen Middle Initial: S Last Name: Roberts Degree(s): MD PhD Organization: Oregon Health and Science University, Portland, OR USA First Name: Min Middle Initial: H Last Name: Kang Degree(s): PharmD Organization: Texas Tech University Health Sciences Center School of Medicine Lubbock, TX, USA First Name: C Patrick Last Name: Reynolds Degree(s): MD PhD Organization: Texas Tech University Health Sciences Center School of Medicine Lubbock, TX, USA
Presenting Author:	C Patrick Reynolds
Institution:	Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX, USA
Email Address:	patrick.reynolds@ttuhsc.edu