Project Funding Details

Title: [Aberrant reactivation of meiosis regulatory genes contributes to genomic instability, carcinogenesis and cancer progression in cutaneous T-cell lymphoma (CTCL)] La réactivation aberrante des gènes régulateurs de la méiose contribue à l’instabilité génomique, à la carcinogenèse et à la progression du cancer dans le lymphome cutané à cellules T (LCCT)
Alt. Award Code: 31640_1
Funding Organization: Fonds de la recherche du Québec – Santé
Budget Dates: 2021-05-31 to 2023-01-30
Principal Investigator: Gill, Raman Preet Kaur
Institution: McGill University Health Centre
Region: North America
Location: Montréal, QC, CA

Collaborators

This project funding has either no collaborators or the information is not available.

Technical Abstract

Lay abstract (no permission to release technical abstract): Le lymphome cutané à cellules T (LCCT) est le lymphome de la peau le plus courant. Malgré les progrès récents, ce lymphome demeure difficile à diagnostiquer (délai de diagnostic ~ 6 ans) car il imite d'autres éruptions cutanées courantes telles que l'eczéma et le psoriasis. Il demeure impossible de prédire quels patients atteints de LCCT à un stade précoce progresseront vers des stades avancés. De plus, LCCT avancé reste difficile à traiter avec une survie médiane de seulement 2 à 4 ans. Par conséquent, de nouveaux marqueurs diagnostiques / pronostiques et de nouvelles cibles thérapeutiques sont nécessaires pour aider à la prise en charge de ce cancer. Les recherches de notre laboratoire indiquent qu'un certain nombre de gènes présents dans les tissus germinaux (testicules et ovaires) sont anormalement ré-exprimés dans LCCT. Nous proposons d'étudier comment la réactivation de ces gènes (par exemple, l'expression et l'activité des gènes régulateurs du cancer des testicules et de la méiose) survient et contribue à l'instabilité génomique, au développement et à la progression du cancer du LCCT. Puisque ces gènes ne sont généralement pas exprimés dans les tissus somatiques sains, leur régulation positive pourrait être utilisée comme marqueur diagnostique. De plus, étant donné que ces gènes favorisent potentiellement la progression du cancer, leur expression à un stade précoce pourrait servir de signe avant-coureur d'une maladie agressive nécessitant une thérapie systémique. Enfin, l'activité de plusieurs de ces gènes est probablement essentielle à la survie des cellules cancéreuses et, par conséquent, leur ciblage pourrait mener à de nouvelles thérapies pour les patients atteints de LCCT. Au cours du projet de recherche proposé, j'étudierai les patrons d'expression et d'activation des gènes impliqués dans la régulation du cancer des testicules et de la méiose, ainsi que leur régulation et leur fonction moléculaire dans LCCT. Aussi, je déterminerai comment ils peuvent être utilisés comme nouveaux marqueurs diagnostiques / pronostiques et exploités comme cibles thérapeutiques. Ce projet identifiera un ensemble fiable de marqueurs qui aideront à 1) raccourcir le délai de diagnostic et à distinguer LCCT des autres éruptions cutanées bénignes ; 2) sélectionner des marqueurs pronostiques qui identifieront les patients à un stade précoce nécessitant des thérapies agressives et 3) définir comment ces gènes / protéines importants pourraient être ciblés pour traiter LCCT.

Public Abstract

See Tech Abstract

Cancer Types

Non-Hodgkin's Lymphoma

Common Scientific Outline (CSO) Research Areas

1.2 Biology Cancer Initiation: Alterations in Chromosomes
4.1 Early Detection, Diagnosis, and Prognosis Technology Development and/or Marker Discovery

Single-funder organizations
Partner	Caveat
ACS	Dollar amounts found in the ICRP database are different than what is reported in the American Cancer Society's Annual Report. The dollar amounts spent on research reported in audited reports include operating expenses of the Research Department. Additionally, the dollar amounts also exclude all grants that were cancelled after being awarded, but include money that was returned from grants cancelled in the current year that were awarded in previous years. The dollar amounts reported in the database are unaudited and include grants awarded each fiscal year, exclusive of grants that cancelled before activation.
CBCRP	The California Breast Cancer Research Program grants are awarded only to individuals or institutions in California. Grants to the University of California receive only direct funds, while grants to other institutions also receive indirect costs (overhead) at 25% or the federally negotiated rate. Collaborative awards are counted in graphs and tables by the number of co-Principal Investigators rather than the number of projects.
Komen	Dollar amounts found in the ICRP database are different than what is reported on Komen\'s website or in Komen\'s Annual Report for the following reasons: Komen commits all funds necessary to support a research grant in the year it is awarded. Therefore, Komen\'s website reports on the full amount of each grant in the year it is initiated, while the ICRP data is annualized, as described. Komen funds research grants to our Scientific Advisors (Scientific Advisory Board members and Komen Scholars) and also provides discretionary funding of research-related projects that are not traditional research grants (e.g. support of the Komen Tissue Bank, ASCO and AACR meeting support). These are included in the overall Research Program spending, as reported in our Annual Report and on our website, but are not included in the ICRP database.
NIH	NIH projects in NIH Reporter assigned to the Spend Category ‘cancer’ are included in the ICRP database from FY2005 onwards. A small number of projects are excluded if essential information is missing (primarily Project title, Institution). Previous years’ data were drawn from the NFRP and may be incomplete. Starting in FY2007 NCI reports funding supplements, etc., for each grant separately instead of including them in the main project, therefore the number of projects may differ significantly from those of previous years. Projects with a cost of $0 include those that were a no-cost extension of the grant or when funding was provided by another NIH institute or center for that FY. NCI dollars in the ICRP database are drawn from NIH reporter and may not match dollars from other NCI-only databases.
Worldwide Cancer Research	Worldwide Cancer Research is unique in that the majority of our funding is awarded to researchers in countries outside the UK. Like many UK research charities, Worldwide Cancer Research only funds the direct costs of research. This creates significant problems in making quantitative comparisons between our funding and that provided by some of the other agencies in the ICRP, which fund both the direct and indirect costs (often called overheads) of research.

UK Organizations that are part of NCRI
Partner	Caveat
NCRI (GENERIC)	NCRI submits data to ICRP on behalf of all UK NCRI members from its Cancer Research Database (CaRD). The database only includes entries where funding can be directly attributed to a set of clearly defined research objectives. This means that the CaRD only contains information on all direct research funding (project, programme, fellowship, unit and institute) financed by NCRI Member organizations, for which an abstract has been submitted and where the project is active in any given financial year (April - March). Examples of funding that are currently outside the scope of CaRD are infrastructure, meeting grants and research management support."
Breakthrough (UK)	The ICRP database includes all Breakthrough Breast Cancer\'s research spend reported through its Annual Reports & Accounts. There is some variance due to different reporting periods (1 April snapshot versus full financial year) meaning that some research spend that is already committed may not be included in the ICRP figures. Expenditure on non-research charitable activities and management support costs are excluded from the NCRI, and by extension, the ICRP dataset. For further information on Breakthrough\'s research please visit www.breakthroughresearch.org.uk or email research@breakthrough.org.uk
CR-UK (UK)	The ICRP database includes around 70% of Cancer Research UK\'s direct research spend per financial year as reported through its Annual Reports & Accounts. There is some variance due to different reporting periods meaning that some direct research spend that is planned for allocation will not be included in the ICRP figures. Expenditure on vital research services, technology transfer, meeting grants, research management support and infrastructure to support Cancer Research UK\'s activities is excluded from the NCRI, and by extension, the ICRP dataset.
Department of Health (UK)	There will always be some variance between the figures available on ICRP and the figures reported publicly by DH. There are two reasons for this. Firstly, there is variance due to different reporting periods (1 April snapshot of ICRP versus full financial year reporting by DH). Secondly, the Department\'s National Institute for Health Research (NIHR) encompasses various expenditure on NHS infrastructure for research relevant to cancer that is not in a format that it is possible to capture for ICRP.
Macmillan (UK)	The ICRP database represents about 90% of Macmillan Cancer Support\'s direct research spend per financial year. There is some variance due to different reporting periods meaning that some direct research spend that is planned for allocation will not be included in the ICRP figures. Expenditure on research management support and infrastructure to support Macmillan Cancer Support\'s activities is excluded from the NCRI, and by extension, the ICRP dataset.
Scottish Government Health Directorates (UK)	Scottish Government is committed to improve the health of the Scottish population and the Chief Scientist\'s Office (CSO) funds across a broad range of relevant disease areas. Overall, 75% of the CSO spend is committed to research infrastructure in NHS Scotland. This and much other research expenditure is therefore outside the NCRI remit and, by extension, the ICRP dataset.

Canadian organizations who are part of the CCRA
Partner	Caveat
CCRA	Caveats/limitations specific to Canadian Cancer Research Alliance organizations can be accessed here.

Difference	Detail	Impact on investment figures
Not all CCRS participating organizations are included in the ICRP.	For the period 2005–2021, CCRA submitted data to the ICRP for 35 organizations and three now defunct multi-funded initiatives (CBCRA, CPCRI, and CTCRI). Note that the Canadian Breast Cancer Research Foundation merged operations with the Canadian Cancer Society in February 2017 and Prostate Cancer Canada merged in 2020. Importantly, Alberta Innovates did not report any research projects for 2020 and 2021 due to staffing constraints. Projects within the CCRS total 30,218, of which 24,129 were reported to ICRP.	Moderate for years 2020 and 2021
Not all CCRS projects are included in the ICRP.	“Related support” grants (i.e., travel awards, workshops/symposia, LOIs, etc.) are not submitted to ICRP, but are included in reports released by CCRA. In addition, equipment/infrastructure grants through the Canada Foundation for Innovation and for other funders where the cancer relevance weighting is less than 80% are not reported to the ICRP, but are included in CCRA reports. Any project with cancer relevance of less than 20% is also not reported to the ICRP.	Moderate
Co-funded projects are listed by the administering organization.	Projects that are co-funded appear under the administering organization and are not duplicated per funder. Within CCRA reports, however, investments are reported by the actual funders.	Minor
ICRP uses a different approach to calculating annual project investment.	CCRA provides ICRP with the project budget (adjusted for cancer relevance) and start and end dates. A pro-rated calculation is used to derive annual investment. Within the CCRS, prorated calculations on the basis of annual project amounts (where those data are available) are used to calculate the annual investment.	Minor
ICRP uses different site coding conventions.	The cancer site/type codes used within the CCRS are different from ICRP site codes so results by site will vary in some instances.	Minor
ICRP has technical limitations.	ICRP has a technical limit of 12 site codes and 8 CSO codes and this requires truncation for a couple of large-scale projects within the CCRS.	Very minor
CCRA provides less descriptive information about its projects to ICRP.	Lay abstracts are submitted by CCRA to the ICRP in lieu of technical abstracts and in their language of origin. For projects without lay abstracts (and there are a significant number of these), only titles are provided. An English translation is provided alongside all French project titles to facilitate use of the search engine.	No impact on investment figures, but limits full functionality of search engine especially for organizations that do not collect/report lay abstracts.