PXD044117

PXD044117 is an original dataset announced via ProteomeXchange.

Title	A revised molecular model of ovarian cancer biomarker CA125 (MUC16) enabled by long-read sequencing
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:40:12.771.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rebecca Whelan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-26 15:09:37	ID requested
1	2024-05-21 09:26:34	announced
⏵ 2	2024-10-22 06:40:18	announced	2024-10-22: Updated project metadata.

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]

submitter keyword: proteomics, ovarian cancer,CA125, biomarker, MUC16, Nanopore sequencing

Rebecca Jean Whelan
contact affiliation	Department of Chemistry, Univeristy of Kansas, Lawrence, KS, USA
contact email	rwhelan1@ku.edu
lab head
Rebecca Whelan
contact affiliation	Department of Chemistry, University of Kansas
contact email	rwhelan1@ku.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044117
     1. Label: PRIDE project
     2. Name: A revised molecular model of ovarian cancer biomarker CA125 (MUC16) enabled by long-read sequencing