LRIG1 gene copy number analysis by ddPCR and correlations to clinical factors in breast cancer.
Biomarkers, Tumor
/ genetics
Breast Neoplasms
/ genetics
Case-Control Studies
Female
Follow-Up Studies
Gene Dosage
Humans
In Situ Hybridization, Fluorescence
Membrane Glycoproteins
/ genetics
Middle Aged
Neoplasm Recurrence, Local
/ genetics
Polymerase Chain Reaction
/ methods
Prognosis
Receptor, ErbB-2
/ genetics
Survival Rate
Breast cancer
Gene copy number
LRIG1
Prognosis
ddPCR
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
24 May 2020
24 May 2020
Historique:
received:
13
12
2019
accepted:
30
04
2020
entrez:
26
5
2020
pubmed:
26
5
2020
medline:
3
2
2021
Statut:
epublish
Résumé
Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) copy number alterations and unbalanced gene recombination events have been reported to occur in breast cancer. Importantly, LRIG1 loss was recently shown to predict early and late relapse in stage I-II breast cancer. We developed droplet digital PCR (ddPCR) assays for the determination of relative LRIG1 copy numbers and used these assays to analyze LRIG1 in twelve healthy individuals, 34 breast tumor samples previously analyzed by fluorescence in situ hybridization (FISH), and 423 breast tumor cytosols. Four of the LRIG1/reference gene assays were found to be precise and robust, showing copy number ratios close to 1 (mean, 0.984; standard deviation, +/- 0.031) among the healthy control population. The correlation between the ddPCR assays and previous FISH results was low, possibly because of the different normalization strategies used. One in 34 breast tumors (2.9%) showed an unbalanced LRIG1 recombination event. LRIG1 copy number ratios were associated with the breast cancer subtype, steroid receptor status, ERBB2 status, tumor grade, and nodal status. Both LRIG1 loss and gain were associated with unfavorable metastasis-free survival; however, they did not remain significant prognostic factors after adjustment for common risk factors in the Cox regression analysis. Furthermore, LRIG1 loss was not significantly associated with survival in stage I and II cases. Although LRIG1 gene aberrations may be important determinants of breast cancer biology, and prognostic markers, the results of this study do not verify an important role for LRIG1 copy number analyses in predicting the risk of relapse in early-stage breast cancer.
Sections du résumé
BACKGROUND
BACKGROUND
Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) copy number alterations and unbalanced gene recombination events have been reported to occur in breast cancer. Importantly, LRIG1 loss was recently shown to predict early and late relapse in stage I-II breast cancer.
METHODS
METHODS
We developed droplet digital PCR (ddPCR) assays for the determination of relative LRIG1 copy numbers and used these assays to analyze LRIG1 in twelve healthy individuals, 34 breast tumor samples previously analyzed by fluorescence in situ hybridization (FISH), and 423 breast tumor cytosols.
RESULTS
RESULTS
Four of the LRIG1/reference gene assays were found to be precise and robust, showing copy number ratios close to 1 (mean, 0.984; standard deviation, +/- 0.031) among the healthy control population. The correlation between the ddPCR assays and previous FISH results was low, possibly because of the different normalization strategies used. One in 34 breast tumors (2.9%) showed an unbalanced LRIG1 recombination event. LRIG1 copy number ratios were associated with the breast cancer subtype, steroid receptor status, ERBB2 status, tumor grade, and nodal status. Both LRIG1 loss and gain were associated with unfavorable metastasis-free survival; however, they did not remain significant prognostic factors after adjustment for common risk factors in the Cox regression analysis. Furthermore, LRIG1 loss was not significantly associated with survival in stage I and II cases.
CONCLUSIONS
CONCLUSIONS
Although LRIG1 gene aberrations may be important determinants of breast cancer biology, and prognostic markers, the results of this study do not verify an important role for LRIG1 copy number analyses in predicting the risk of relapse in early-stage breast cancer.
Identifiants
pubmed: 32448168
doi: 10.1186/s12885-020-06919-w
pii: 10.1186/s12885-020-06919-w
pmc: PMC7245921
doi:
Substances chimiques
Biomarkers, Tumor
0
LRIG1 protein, human
0
Membrane Glycoproteins
0
Receptor, ErbB-2
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
459Subventions
Organisme : Cancer Research Foundation in Northern Sweden
ID : LP 16 2139
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