Page 51 - SDIR5 Abstract book 21 12 2021.

POSTER PRESENTATIONS

P11

Role of TP53 and PTEN tumor suppressor genes alterations in breast cancer response to
therapy

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Milica Nedeljković , Tatjana Dramićanin , Mirjana Prvanović , Blagoje Murganić , Tijana Tomić , Neila
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Ademović , Zorka Milovanović ,Nikola Tanić , Nasta Tanić
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1 Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia
2 Institute of Nuclear Sciences „Vinča“,University of Belgrade, p.fah 522, 11001 Belgrade, Serbia
3 Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
4 Institute for Biological Research „Siniša Stanković“, University of Belgrade, Blvd. Despota Stefana 142,
11000 Belgrade, Serbia

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.
Key words: PTEN, TP53, therapy response, survival, breast cancer

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