Role of TP53 and PTEN tumor suppressor genes alterations in breast cancer response to therapy
2021
Authors:
Nedeljković, MilicaDramićanin, Tatjana
Prvanović, Mirjana
Murganić, Blagoje
Tomić, Tijana
Ademović, Nejla
Milovanović, Zorka
Tanić, Nikola
Tanić, Nasta
Contributors
Đorđić-Crnogorac, MarijaNedeljković, Milica
Document Type:
Conference object (Published version)
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© 2021 Srpsko društvo istraživača raka
Metadata
Show full item recordAbstract:
Background: Breast cancer (BC) is the most frequent type of malignancy and the leading cause of cancer related death among women worldwide. Multiple interconnected factors determine BC response to therapy and clinical outcome. TP53 and PTEN are the most frequently altered tumor suppressor genes (TSGs) in human cancers. Material and methods: To determine the potential influence of TSGs on the response to therapy we analyzed alterations of TP53 and PTEN in 90 BC specimens. The specimens were stratified based on systemic adjuvant therapy (hormonal therapy only (HT), HT and chemotherapy (HT/CHT), HT/CHT and biological therapy (HT/CHT/H). Functional inactivation of TP53 by mutations and/or loss of heterozygosity (LOH) and PTEN by LOH and/or promoter hypermethylation, were tested using single-strand conformational polymorphism (SSCP) analysis, gene sequencing, fragment analysis and methylation-specific PCR (MS-PCR) methods respectively. Results: Altered TP53 was found in 63/90 specimens (70%) while 54/90 (60%) had inactivated PTEN. Inactivation of PTEN was more frequent in tumors with altered TP53. Patients with altered TP53, lived shorter (p=0.0007) compared to those with wild type (wt) gene. The survival of patients with both TSGs altered was shorter compared to wt genes (p=0.024). Patients with wtTP53 treated with HT had longer survival (p=0.000001) when compared to all other groups. Women with both TSGs altered who received tamoxifen lived shorter than those on HT with both/one TSGs intact (p = 0.03). Conclusion: Patients with wtTP53 showed significantly better therapy response regardless of type of therapy, compared to carriers of altered TP53.
Keywords:
PTEN; TP53; therapy response; survival; breast cancerFunding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
In:
- Đorđević Crnogorac M, Nedeljković M, editors. Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event. Beograd: Srpsko društvo istraživača raka; 2021.p. 38.