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Mutations and Target Genes in Adenoid Cystic Carcinoma

Award Number: R01DE023222
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/10/2012
PERIOD OF PERFORMANCE END DATE: 02/29/2028

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Mutations and Target Genes in Adenoid Cystic Carcinoma - Project Summary/Abstract Adenoid Cystic Carcinoma (ACC) is the second most common type of salivary gland tumor, but can also arise in other tissues such as lacrimal gland, breast and skin. ACC tumors display heterogeneous morphology and have a variable clinical course. Many ACC patients survive 10 years or more after the standard therapy of surgery and radiation, but a fraction succumb much more quickly and others acquire distant metastases or relapse 5 or more years after the initial treatment. So patients often have to endure significant morbidity including reconstructive surgery while living under the threat of recurrence for decades. ACC is one of the only human tumors in which mutations involving the MYB oncogene are known to be the most common driver. A large fraction of ACC tumors harbor a t(6;9) translocation, which juxtaposes an enhancer from the NFIB gene on chromosome 9p close to the MYB oncogene on chromosome 6q. However, ACC tumors have heterogeneous molecular characteristics. About half the tumors that express MYB harbor translocations that fuse the MYB and NFIB genes, resulting in a ‘broken’ or truncated MYB gene that can only express Myb proteins with C-terminal truncations – mutations that are known to activate the oncogenic potential of the Myb transcription factor. But the remaining MYB positive tumors appear to express full-length Myb proteins without any fusion to NFIB. And some tumors harbor different translocations that position the MYB gene close to other enhancers or that involve the related MYBL1 gene instead of MYB. This molecular heterogeneity is also reflected in the subgroups of ACC patients that have been identified by gene expression profiling, including at least one poor-prognosis subgroup with a unique gene expression profile and another subgroup that expresses neither MYB nor MYBL1 and must harbor as yet unidentified driver mutations. Deciphering the molecular events that lead to ACC has been complicated by the lack of adequate cell models for this tumor. To avoid any issues from highly selected or mislabeled cell lines, our strategy has been to utilize primary salivary gland ACC patient samples, an approach that has led to numerous important results that have reshaped our understanding of ACC tumors. In this competing renewal application we will generate the largest set of ACC tumor RNA-seq data in order to move the field forward in several ways. We will address the heterogeneity of ACC tumors and patients, set the stage for the development of new therapeutic strategies that target Myb proteins, use patient samples in a translational way to validate experimental results about Myb protein biology and we will begin migrating our approaches to clinical (CLIA) laboratories to make them usable in the clinic.


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: 2025 ( Subtotal = $431,067 )
2025	2025	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	001	12	5/7/2025	NON-COMPETING CONTINUATION	$43,106
2025	2025	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	000	12	2/28/2025	NON-COMPETING CONTINUATION	$387,961
														Subtotal = $431,067

Issue Date FY: 2024 ( Subtotal = $428,710 )
2024	2024	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	000	11	1/17/2024	NON-COMPETING CONTINUATION	$393,714
2024	2024	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	001	11	5/30/2024	NON-COMPETING CONTINUATION	$34,996
2024	2023	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	003	10	9/27/2024	COMPETING CONTINUATION	$23
2024	2021	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	002	9	9/27/2024	NON-COMPETING CONTINUATION	-$23
														Subtotal = $428,710

Issue Date FY: 2023 ( Subtotal = $445,398 )
2023	2023	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	001	10	3/10/2023	COMPETING CONTINUATION	$445,398
2023	2023	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	002	10	7/17/2023	COMPETING CONTINUATION	$0
2023	2021	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	000	9	3/3/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $445,398

Issue Date FY: 2021 ( Subtotal = $359,813 )
2021	2021	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	000	9	7/20/2021	NON-COMPETING CONTINUATION	$359,813
														Subtotal = $359,813

Issue Date FY: 2020 ( Subtotal = $359,813 )
2020	2020	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	000	8	7/15/2020	NON-COMPETING CONTINUATION	$359,813
														Subtotal = $359,813

Issue Date FY: 2019 ( Subtotal = $359,813 )
2019	2019	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	000	7	7/23/2019	NON-COMPETING CONTINUATION	$359,813
														Subtotal = $359,813

Issue Date FY: 2018 ( Subtotal = $359,813 )
2018	2018	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	001	6	7/31/2018	NON-COMPETING CONTINUATION	$359,813
2018	2015	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	000	4	2/5/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $359,813

Issue Date FY: 2017 ( Subtotal = $359,813 )
2017	2017	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	001	5	7/10/2017	COMPETING CONTINUATION	$359,813
2017	2015	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	000	4	10/27/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $359,813

Issue Date FY: 2015 ( Subtotal = $497,987 )
2015	2015	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	000	4	8/26/2015	NON-COMPETING CONTINUATION	$497,987
														Subtotal = $497,987

Issue Date FY: 2014 ( Subtotal = $671,168 )
2014	2014	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	000	2	6/10/2014	SUPPLEMENT FOR EXPANSION	$9,859
2014	2014	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	002	3	9/2/2014	SUPPLEMENT FOR EXPANSION	$163,350
2014	2014	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	001	3	8/19/2014	NON-COMPETING CONTINUATION	$497,959
														Subtotal = $671,168

Issue Date FY: 2013 ( Subtotal = $424,914 )
2013	2013	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	000	2	8/2/2013	NON-COMPETING CONTINUATION	$424,914
														Subtotal = $424,914

Issue Date FY: 2012 ( Subtotal = $450,117 )
2012	2012	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Oral Diseases and Disorders Research	000	1	9/7/2012	NEW	$450,117
														Subtotal = $450,117

Grand Total All Awards = $5,148,426

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Mutations and Target Genes in Adenoid Cystic Carcinoma

Award Number: R01DE023222

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/10/2012

PERIOD OF PERFORMANCE END DATE: 02/29/2028

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