Evidence map›Paper›PMID 32393398›Full record

ArticleBreast cancer research : BCR2020

Functional evaluation of five BRCA2 unclassified variants identified in a Sri Lankan cohort with inherited cancer syndromes using a mouse embryonic stem cell-based assay.

Nirmala Sirisena, Kajal Biswas, Teresa Sullivan, Stacey Stauffer, Linda Cleveland, Eileen Southon, Vajira H W Dissanayake, Shyam K Sharan

Open access · goldAbstract readEvaluation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research : BCR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 7 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Nirmala SirisenaHuman Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, 8, Sri Lanka.ORCID 0000-0003-0994-6954
Kajal BiswasMouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Bldg 560, Room 32-33, 1050 Boyles Street, Frederick, MD, 21702, USA.
Teresa SullivanMouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Bldg 560, Room 32-33, 1050 Boyles Street, Frederick, MD, 21702, USA.
Stacey StaufferMouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Bldg 560, Room 32-33, 1050 Boyles Street, Frederick, MD, 21702, USA.
Linda ClevelandMouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Bldg 560, Room 32-33, 1050 Boyles Street, Frederick, MD, 21702, USA.
Eileen SouthonMouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Bldg 560, Room 32-33, 1050 Boyles Street, Frederick, MD, 21702, USA.
Vajira H W DissanayakeHuman Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, 8, Sri Lanka.ORCID 0000-0002-3264-6856
Shyam K SharanMouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Bldg 560, Room 32-33, 1050 Boyles Street, Frederick, MD, 21702, USA. sharans@mail.nih.gov.ORCID 0000-0002-9333-870X
Frederick National Laboratory for Cancer Research · USUniversity of Colombo · LK

Funding

Functional Evaluation of BRCA2 Variants on TumorigenesisZIABC010387 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SHARAN, SHYAM · 2009 to 2025
$12.5M
Functional Analysis of Variants Identified in Human Breast Cancer SusceptibilityZIABC011181 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SHARAN, SHYAM · 2009 to 2025
$11.6M
NCI NIH HHS Intramural Research Program
6 · The paper itself

Abstract

Next-generation sequencing of Sri Lankan families with inherited cancer syndromes resulted in the identification of five BRCA2 variants of unknown clinical significance. Interpreting such variants poses significant challenges for both clinicians and patients. Using a mouse embryonic stem cell-based functional assay, we found I785V, N830D, and K2077N to be functionally indistinguishable from wild-type BRCA2. Specific but mild sensitivity to olaparib and reduction in homologous recombination (HR) efficiency suggest partial loss of function of the A262T variant. This variant is located in the N-terminal DNA binding domain of BRCA2 that can facilitate HR by binding to dsDNA/ssDNA junctions. P3039P is clearly pathogenic because of premature protein truncation caused by exon 23 skipping. These findings highlight the value of mouse embryonic stem cell-based assays for determining the functional significance of variants of unknown clinical significance and provide valuable information regarding risk estimation and genetic counseling of families carrying these BRCA2 variants.

Indexed as

MutationAnimalsBiological AssayBRCA2 ProteinBreast NeoplasmsCell SurvivalCohort StudiesFemaleHomologous RecombinationHumansMiceMouse Embryonic Stem CellsNeoplastic Syndromes, HereditarySri LankaXenograft Model Antitumor AssaysBRCA2 ProteinBRCA2 protein, humanBRCA2ClassificationFunctional assayInherited cancerNext-generation sequencingVariants of unknown clinical significance (VUS)

Identifiers

PMID32393398
PMCPMC7216543
OpenAlexW3025456249

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.