ID

46133

Description

Principal Investigator: Theodora S. Ross, MD, PhD, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA, and Department of Cancer Genetics, UT Southwestern Medical Center, Dallas, TX, USA MeSH: Neoplasms,Breast Neoplasms,Ovarian Neoplasms,Peritoneal Neoplasms,Skin Neoplasms,Esophageal Neoplasms,Thyroid Neoplasms,Urinary Bladder Neoplasms,Endometrial Neoplasms,Fallopian Tube Neoplasms,Melanoma,Testicular Neoplasms,Bile Duct Neoplasms,Lung Neoplasms,Colonic Neoplasms,Adrenocortical Carcinoma,Carcinoma, Renal Cell,Colonic Polyps,Adenomatous Polyposis Coli,Lymphoma, Large B-Cell, Diffuse,Pheochromocytoma,Paraganglioma,Leiomyoma,Hemangioblastoma,Hyperparathyroidism,Pancreatic Neoplasms,Vulvar Neoplasms,Brain Neoplasms,Liver Neoplasms,Kidney Neoplasms,Prostatic Neoplasms,Glioblastoma,Oncocytoma, renal https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000942 Despite the potential of whole-genome sequencing (WGS) to improve patient diagnosis and care, the empirical value of WGS in the cancer genetics clinic is unknown. We performed WGS on members of two cohorts of cancer genetics patients: those with BRCA1/2 mutations (n = 176) and those without (n = 82). Initial analysis of potentially pathogenic variants (PPVs, defined as nonsynonymous variants with allele frequency 1% in ESP6500) in 163 clinically-relevant genes suggested that WGS will provide useful clinical results. This is despite the fact that a majority of PPVs were novel missense variants likely to be classified as variants of unknown significance (VUS). Furthermore, previously reported pathogenic missense variants did not always associate with their predicted diseases in our patients. This suggests that the clinical use of WGS will require large-scale efforts to consolidate WGS and patient data to improve accuracy of interpretation of rare variants. While loss-of-function (LoF) variants represented only a small fraction of PPVs, WGS identified additional cancer risk LoF PPVs in patients with known BRCA1/2 mutations and led to cancer risk diagnoses in 21% of non-BRCA cancer genetics patients after expanding our analysis to 3209 ClinVar genes. These data illustrate how WGS can be used to improve our ability to discover patients' cancer genetic risks. "Reprinted from doi:10.1016/j.ebiom.2014.12.003, with permission from EBioMedicine."

Link

dbGaP study id = phs000942

Keywords

  1. 11/27/24 11/27/24 - Dr. Christian Niklas
Copyright Holder

Theodora S. Ross, MD, PhD, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA, and Department of Cancer Genetics, UT Southwestern Medical Center, Dallas, TX, USA

Uploaded on

November 27, 2024

DOI

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License

Creative Commons BY 4.0

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dbGaP phs000942 Use of WGS for Diagnosis and Discovery in the Cancer Genetics Clinic

Subject ID, sample ID, sample source, source sample ID, and sample use variable of participants with or without different types of cancer and involved in the "Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic" project.

pht004835
Description

pht004835

Subject ID
Description

SUBJECT_ID

Data type

text

Alias
UMLS CUI [1,1]
C2348585
Sample ID
Description

SAMPLE_ID

Data type

text

Alias
UMLS CUI [1,1]
C1299222
Source repository where samples originate [Ohio State University, University of Texas Southwestern Medical Center, Coriell]
Description

SAMPLE_SOURCE

Data type

string

Alias
UMLS CUI [1,1]
C3847505
UMLS CUI [1,2]
C0449416
UMLS CUI [1,3]
C2347026
Sample ID used in the Source Repository
Description

SOURCE_SAMPLE_ID

Data type

text

Alias
UMLS CUI [1,1]
C1299222
UMLS CUI [1,2]
C3847505
UMLS CUI [1,3]
C0449416
Sample Use
Description

SAMPLE_USE

Data type

string

Alias
UMLS CUI [1,1]
C2347026
UMLS CUI [1,2]
C1524063

Similar models

Subject ID, sample ID, sample source, source sample ID, and sample use variable of participants with or without different types of cancer and involved in the "Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic" project.

Name
Type
Description | Question | Decode (Coded Value)
Data type
Alias
Item Group
pht004835
SUBJECT_ID
Item
Subject ID
text
C2348585 (UMLS CUI [1,1])
SAMPLE_ID
Item
Sample ID
text
C1299222 (UMLS CUI [1,1])
SAMPLE_SOURCE
Item
Source repository where samples originate [Ohio State University, University of Texas Southwestern Medical Center, Coriell]
string
C3847505 (UMLS CUI [1,1])
C0449416 (UMLS CUI [1,2])
C2347026 (UMLS CUI [1,3])
SOURCE_SAMPLE_ID
Item
Sample ID used in the Source Repository
text
C1299222 (UMLS CUI [1,1])
C3847505 (UMLS CUI [1,2])
C0449416 (UMLS CUI [1,3])
Item
Sample Use
string
C2347026 (UMLS CUI [1,1])
C1524063 (UMLS CUI [1,2])
Code List
Sample Use
CL Item
SNP and CNV genotypes derived from sequence data (Seq_DNA_SNP_CNV)
C0017431 (UMLS CUI [1,1])

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