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PXD044117

PXD044117 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA revised molecular model of ovarian cancer biomarker CA125 (MUC16) enabled by long-read sequencing
DescriptionThe biomarker CA125, a peptide epitope located in several tandem repeats of the mucin MUC16, is the gold-standard for monitoring regression and recurrence of high-grade serous ovarian cancer in response to therapy. However, the CA125 epitope along with several structural features of the MUC16 molecule are ill-defined. One central aspect still unresolved is the number of tandem repeats in MUC16 and how many of these contain the CA125 epitope. Studies from the early 2000s assembled short DNA reads to estimate that MUC16 contained 63 repeats. Here, we conduct Nanopore long-read sequencing of MUC16 transcripts from three primary ovarian tumors and established cell lines (OVCAR3, OVCAR5, and Kuramochi) for a more exhaustive and accurate estimation and sequencing of the MUC16 tandem repeats. The consensus sequence derived from these six sources was confirmed by proteomics validation and agrees with recent additions to the NCBI database. We propose a model of MUC16 containing 19—not 63—tandem repeats. Additionally, we predict the structure of the tandem repeat domain using the deep-learning algorithm, AlphaFold. The predicted structure displays an SEA domain and unstructured linker region rich in proline, serine, and threonine residues in all 19 tandem repeats. Our studies now pave the way for a detailed characterization of the CA125 epitope. Sequencing and modeling of the MUC16 tandem repeats along with their glycoproteomic characterization, currently underway in our laboratories, will help identify novel epitopes in the MUC16 molecule that improve on the sensitivity and clinical utility of the current CA125 assay.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:40:12.771.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRebecca Whelan
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-07-26 15:09:37ID requested
12024-05-21 09:26:34announced
22024-10-22 06:40:18announced2024-10-22: Updated project metadata.
Publication List
10.1158/2767-9764.crc-23-0327;
Wang CW, Weaver SD, Boonpattrawong N, Schuster-Little N, Patankar M, Whelan RJ, A Revised Molecular Model of Ovarian Cancer Biomarker CA125 (MUC16) Enabled by Long-read Sequencing. Cancer Res Commun, 4(1):253-263(2024) [pubmed]
Keyword List
submitter keyword: proteomics, ovarian cancer,CA125, biomarker, MUC16, Nanopore sequencing
Contact List
Rebecca Jean Whelan
contact affiliationDepartment of Chemistry, Univeristy of Kansas, Lawrence, KS, USA
contact emailrwhelan1@ku.edu
lab head
Rebecca Whelan
contact affiliationDepartment of Chemistry, University of Kansas
contact emailrwhelan1@ku.edu
dataset submitter
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