PXD048272-1

PXD048272 is an original dataset announced via ProteomeXchange.

Title	Mapping in silico genetic networks of tumour suppressor gene to uncover novel functional associations and cancer cell vulnerabilities
Description	Cancers harbouring loss-of-function (LOF) alterations in tumour suppressor genes lack targeted therapies, thus alternative means to characterise gene function and identify vulnerabilities in these cancer cells are required. Here, we map the in silico genetic networks of KMT2D, a frequently mutated tumour suppressor gene, to demonstrate its utility in uncovering novel functional associations and vulnerabilities in cancer cells with tumour suppressor gene LOF alterations. In silico KMT2D networks revealed associated with histone modification, DNA replication, metabolism, and immune response. We identified synthetic lethal (SL) candidates encoding exising therapeutic targets. Analysing patient data from The Cancer Genome Atlas (TCGA) and the Personalized OncoGenomics Project (NCT021556210), we showed dysregulated pathways associated with SL candidates and elevated immune checkpoint response markers in KMT2DLOF cases, bringing forth evidence supporting KMT2D as a biomarker for immune checkpoint inhibitors. Our study presents a framework for identifying targetable vulnerabilities in cancers with tumour suppressor gene alterations.
HostingRepository	PRIDE
AnnounceDate	2024-10-18
AnnouncementXML	Submission_2024-10-18_04:58:50.371.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christopher Hughes
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C labeled residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-05 03:27:18	ID requested
⏵ 1	2024-10-18 04:58:50	announced

Dataset with its publication pending

submitter keyword: metabolism,KMT2D, immune checkpoint inhibitor, genetic networks, synthetic lethality

Christopher Hughes
contact affiliation	Manager Biological Mass Spectrometry Core Dalhousie University
contact email	christopher.hughes@dal.ca
lab head
Christopher Hughes
contact affiliation	Dalhousie University
contact email	christopher.hughes@dal.ca
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/10/PXD048272

PRIDE project URI

• PRIDE
  1. PXD048272
     1. Label: PRIDE project
     2. Name: Mapping in silico genetic networks of tumour suppressor gene to uncover novel functional associations and cancer cell vulnerabilities