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Parathyroid Tumor Clonal Status as a Biomarker in Primary Hyperparathyroidism

Award Number: R01CA228399
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2018
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Parathyroid Tumor Clonal Status as a Biomarker in Primary Hyperparathyroidism - Project Summary/Abstract Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia in ambulatory patients, and may lead to bone loss and fracture, cardiovascular disease, kidney stones, and neurocognitive impairment (1). PHPT is the third most common endocrine disorder with an annual incidence between 34 to 120 per 100,000 person-years that is rising, especially among postmenopausal women. Since the first description of PHPT and its surgical treatment in the 1920s, the pathogenesis of PHPT has been viewed simply: A parathyroid tumor develops from a single transformed clone (i.e. monoclonal) that expands and secretes excessive PTH causing hypercalcemia and the symptoms and sequellae of PHPT. This paradigm predicts that PHPT develops from a single tumor (single gland disease, SGD) and that removal of this single tumor by parathyroidectomy (PTX) cures the disease. Although conceptually attractive, this simple approach does not explain several observations including: 1. The presence of multiple gland disease (MGD) in up to 20% of PHPT patients; 2. The observation that PTH remains elevated following PTX in up to 30% of patients; 3. The reality that symptoms and sequellae of PHPT often do not improve following PTX; and 4. The development of recurrent PHPT in up to 15% of patients (2). These observations, combined with data from our laboratory describing the molecular heterogeneity of parathyroid tumors have led us to suspect that PHPT may represent several different diseases that can be distinguished based on characteristics of the parathyroid tumor. The foundation for the proposed work has been published by our group in two studies. Our first study characterized isolated parathyroid cells from parathyroid adenomas in PHPT and showed that a significant proportion (40%, 5/14) of these tumors were comprised of multiple clones (i.e. polyclonal). Our second study of 119 patients confirmed that up to 46% of PHPT patients have polyclonal tumors and that the clonal status (i.e. monoclonal versus polyclonal) of the tumor predicts MGD that is often missed at surgery. These findings support the premise that parathyroid tumor clonal status reflects different types of PHPT with different etiologies, disease presentation and treatment outcomes. We now propose to characterize PHPT patients with these tumor types and test the novel hypothesis that PHPT can better be understood and treated by classifying the disorder in terms of the clonal status of the underlying parathyroid tumor.


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 = $0 )
2025	2023	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Cancer Detection and Diagnosis Research	001	5	2/12/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2023	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Cancer Detection and Diagnosis Research	000	5	12/13/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $662,448 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Cancer Detection and Diagnosis Research	004	5	5/30/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$688,102
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Cancer Detection and Diagnosis Research	001	5	3/6/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$662,448
2023	2022	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	000	4	3/6/2023	NON-COMPETING CONTINUATION	$0
2023	2022	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	003	4	5/30/2023	NON-COMPETING CONTINUATION	-$551,631
2023	2021	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	002	3	5/30/2023	NON-COMPETING CONTINUATION	-$136,471
														Subtotal = $662,448

Issue Date FY: 2022 ( Subtotal = $551,631 )
2022	2022	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	001	4	5/19/2022	NON-COMPETING CONTINUATION	$45,032
2022	2022	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	000	4	11/10/2021	NON-COMPETING CONTINUATION	$506,599
														Subtotal = $551,631

Issue Date FY: 2021 ( Subtotal = $622,913 )
2021	2021	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	000	3	11/6/2020	NON-COMPETING CONTINUATION	$591,767
2021	2021	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	001	3	1/22/2021	NON-COMPETING CONTINUATION	$31,146
														Subtotal = $622,913

Issue Date FY: 2020 ( Subtotal = $634,474 )
2020	2020	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	001	2	1/15/2020	NON-COMPETING CONTINUATION	$63,449
2020	2020	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	000	2	11/13/2019	NON-COMPETING CONTINUATION	$571,025
														Subtotal = $634,474

Issue Date FY: 2019 ( Subtotal = $700,756 )
2019	2019	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	001	1	2/18/2019	NEW	$1,543
2019	2019	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	000	1	11/23/2018	NEW	$699,213
														Subtotal = $700,756

Grand Total All Awards = $3,172,222

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Parathyroid Tumor Clonal Status as a Biomarker in Primary Hyperparathyroidism

Award Number: R01CA228399

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2018

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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