The Role of TP53 and PTEN tumor suppressor genes in response to different breast cancer treatment modalities
Улога ТП53 и ПТЕН тумор супресор гена у одговору на различите модалитете терапије канцера дојке
2022
Аутори:
Tanić, NikolaDramićanin, Tatjana
Milovanović, Zorka
Nedeljković, Milica
Tomić, Tijana
Ademović, Nejla
Murganić, Blagoje
Tanic, Nasta
Остала ауторства
Arsenijević, NebojšaТип документа:
Конференцијски прилог (Објављена верзија)
,
© 2022 by the Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
Метаподаци
Приказ свих података о документуАпстракт:
Breast cancer (BC) is the most frequent type of malignancy and the leading cause
of cancer related death among women worldwide. More than 70% of all diagnosed invasive
BCs express steroid receptors and, as such, are subjected to endocrine therapy.
BC is exceptionally heterogeneous disease and therefore distinct treatment modalities
are necessary to address these differences. The aim of our study was to investigate
the impact of TP53 and PTEN tumor suppressor genes (TSGs) inactivation on BC
response to different treatment modalities, as well as, their possible cooperation, on
post-operative BC samples. To that end the patients were classified, based on applied
adjuvant therapy, into four distinct groups: those that received hormonal therapy
(HT) only, hormonal therapy combined with chemotherapy (HT/CHT), hormonal
therapy combined with chemo and biological therapy (HT/CHT/H), and other systemic
therapies that exclude HT (for example CHT or H). Functional inactivation of
TP53 and PTEN TSG’s were studied by mutation, loss of heterozygosity (LOH) and
hypermethylatyon analysis. Our results revealed that TP53 gene was altered in 63 out
of 90 specimens (70%), while the frequency of PTEN alterations was slightly lower,
54 out of 90 (60%) patients had inactivated PTEN. Simultaneous inactivation was
detected in 43 tested samples (48%) with significant association between two analyzed
TSGs. Further, we found that TP53 status has significant influence on patients’
therapy response. Patients with wild type TP53 show significantly better therapy response
regardless of the type of therapy, compared to carriers of altered p53 gene. In
support of this we showed that hormonally treated women with intact (wt) TP53 gene
had significantly longer survival rate (p=0.000001) when compared to: (i) hormonally
treated women with aberrant TP53gene, (ii) women with intact (wt) p53 subjected to
any of remaining three therapy combinations, and (iii) women with altered TP53 that
belong to second (HT/CHT), third (HT/CHT/H) or forth (systemic Th that exclude
HT) therapy group. Contrary to this, no significance was found between mutational status of PTEN and various treatment modalities. However, significant association
was found between the type of applied therapy and simultaneous alterations of these
two TSGs (p=0.00001).
Кључне речи:
breast cancer; therapy; TP53; PTENФинансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
У:
- Arsenijević N, editor. Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine; 2022. p. 94-7.