Thesis

Pooled Whole-genome CRISPR/Cas12a Loss-of-Function Screens Reveal A Novel Precision Therapeutic Opportunity for Atypical Teratoid/Rhabdoid Tumors

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Though rare, atypical teratoid/rhabdoid tumors (ATRT) remain a clinically challenging pediatric tumor
and lack defined treatments. “One-size-fits-all” multimodal regimens have largely been of modest
clinical benefits thereby urging the development of precision medicine for ATRT. However, the single-
mutation nature of pediatric tumors like ATRT has misrepresented the potential of non-mutated
pathways as viable therapeutic targets. Whole-genome CRISPR loss-of-function screens are a means of
identifying genetic dependencies—an emerging concept that studies the relevance of the whole-
genome towards the survival of a tumor—and therefore represent a powerful tool of identifying novel
therapeutic targets for ATRT. For the first time, pooled whole-genome CRISPR/Cas12a screens were
carried out on ATRT cell lines to reveal ATRT-specific biological vulnerabilities. With the increasing
evidence of serum-induced phenotypic alterations among central nervous system (CNS) tumor lines,
screens were also carried out in serum-free conditions for the first time. Remarkable dependency on
the mitochondrial oxidative phosphorylation (OXPHOS) assembly is herein reported exclusive to ATRT,
suggesting OXPHOS assembly as a potential precision therapeutic target for ATRT.

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Availability

Detail Information

Series Title

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Call Number

BM 24-027

Publisher

i3L, Jakarta : i3L Press., 2024

Collation

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Language

English

ISBN/ISSN

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Classification

NONE

Content Type

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Media Type

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Carrier Type

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Edition

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Subject(s)

Precision Medicine
atypical teratoid/rhabdoid tumor
CRISPR loss-of-function screen
genetic dependency
oxidative phosphorylation

Specific Detail Info

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Statement of Responsibility

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