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The role and mechanism of alternative RNA splice variants and gene fusions as drivers of cancer

Award Number: R35CA253119
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/21/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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The role and mechanism of alternative RNA splice variants and gene fusions as drivers of cancer - Abstract My lab has been the leader in the field of mouse modeling for brain tumors over the past 15 years. We have developed a suite of genetically engineered mouse models that are demonstrably representative of human gliomas and other tumor types. These models have been used to inform treatment options for clinical agents, and this now enables us to propose these models are suitable testbeds for testing potential major improvements to how these diseases are treated. We have three projects. 1) We are understanding the central role of specific splice variants of TrkB in embryonic development and oncogenesis throughout the body. The RCAS modeling system has been used here to show that forced expression of the embryonic splice variant in adult tissues leads to cancer formation broadly. In this project we will investigate the mechanisms of oncogenesis for this splice variant and determine if it could be a good diagnostic or therapeutic target. 2) We are now using the modeling system developed for glioma to address the biology of rare tumors driven by gene fusions. In this grant we propose to understand the mechanisms of oncogenesis for YAP1 gene fusions in the rare tumors ependymoma, porocarcinoma and aggressive meningioma (all for which we have YAP1 gene fusion driven models currently). 3) And, we will use these mouse models to study therapeutic response and identify therapeutic strategies for these fusion driven tumors including identification of FDA approved drugs that would intervene downstream of the action of the gene fusion.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $1,055,493 )
2026	2026	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	001	7	8/14/2026	NON-COMPETING CONTINUATION	$1,055,493
2026	2025	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	000	6	12/5/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $1,055,493

Issue Date FY: 2025 ( Subtotal = $1,212,780 )
2025	2025	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	001	6	8/15/2025	SUPPLEMENT FOR EXPANSION	$78,390
2025	2025	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	000	6	8/11/2025	NON-COMPETING CONTINUATION	$1,056,000
2025	2025	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	002	6	8/18/2025	SUPPLEMENT FOR EXPANSION	$78,390
														Subtotal = $1,212,780

Issue Date FY: 2024 ( Subtotal = $1,117,756 )
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	003	5	8/19/2024	SUPPLEMENT FOR EXPANSION	$78,390
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	002	5	8/15/2024	SUPPLEMENT FOR EXPANSION	$78,390
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	001	5	8/14/2024	NON-COMPETING CONTINUATION	$960,976
2024	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	000	3	12/21/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,117,756

Issue Date FY: 2023 ( Subtotal = $839,885 )
2023	2023	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	001	4	9/11/2023	NON-COMPETING CONTINUATION	$839,885
2023	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	000	3	7/17/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $839,885

Issue Date FY: 2022 ( Subtotal = $1,223,908 )
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	005	3	8/23/2022	NON-COMPETING CONTINUATION	$1,034,880
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	002	2	6/30/2022	SUPPLEMENT FOR EXPANSION	$60,715
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	006	3	8/24/2022	SUPPLEMENT FOR EXPANSION	$128,313
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	004	1	8/15/2022	NEW	$0
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	000	1	5/31/2022	NEW	-$570,838
2022	2021	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	001	2	5/31/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$570,838
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	003	1	7/12/2022	NEW	$0
														Subtotal = $1,223,908

Issue Date FY: 2021 ( Subtotal = $1,056,000 )
2021	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	000	1	9/21/2021	NEW	$1,056,000
														Subtotal = $1,056,000

Grand Total All Awards = $6,505,822

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The role and mechanism of alternative RNA splice variants and gene fusions as drivers of cancer

Award Number: R35CA253119

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/21/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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