Title
HER2 and c-MYC mutational status and INK4a/ARF methylation status in tumors, tumor margins and unaffected oral mucosa of patients with oral squamous cell carcinoma
Creator
Aljabu, Najeeb Mohamed Mohamed, 1964-
Copyright date
2018
Object Links
Select license
Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)
License description
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Language
English
Cobiss-ID
Theses Type
Doktorska disertacija
description
Datum odbrane: 08.10.2018.
Other responsibilities
mentor
Milašin, Jelena, 1957-
mentor
Stamenković-Radak, Marina, 1958-
član komisije
Zeljić, Katarina
član komisije
Milašin, Jelena, 1957-
član komisije
Stamenković-Radak, Marina, 1958-
Academic Expertise
Prirodno-matematičke nauke
Academic Title
-
University
Univerzitet u Beogradu
Faculty
Biološki fakultet
Alternative title
Mutacioni status HER2 i c-MYC gena i metilacioni status INK4a/ARF lokusa u tumoru, tumorskoj margini i neizmenjenoj oralnoj sluzokoži skvamocelularnog karcinoma usne duplje
Publisher
[N. M. M. Aljabu]
Format
106, [12] listova
description
Biology - Genetics / Biologija
- Genetika
Abstract (en)
The development of malignant diseases is due to the accumulation of genetic and
epigenetic changes. Oral squamous cell carcinoma (OSCC) is an aggressive and very common
malignancy of the oral cavity. Patho-histological methods lack sensitivity in terms of the
evaluation of the risk of OSCC recurrence and metastases. This issue can potentially be
overcome by assessing molecular changes in OSCC and its margins.
Aims: (a) to determine the presence of oncogene amplification (c-MYC and HER2) and tumor
suppressor gene methylation (P14 and P16) in tumor, tumor margin and healthy oral mucosa of
patients with OSCC; (b) establish a potential association between molecular and clinical
parameters.
Material and methods: DNA was isolated from tumor, margin and oral mucosa tissue of 40
patients with OSCC, operated at the Clinic for Maxillofacial Surgery, School of Dental
Medicine. The presence of C-MYC and HER2 gene amplification was determined by real-time
PCR, and P14 and P16 methylation by methyl-specific PCR. Statistical analysis with SPSS was
applied to estimate the association between molecular and clinical findings.
Results: Tumor tissues showed the highest prevalence of alterations and oral mucosa the lowest.
Multiple alterations were significantly more frequent in tumors and tumor margins compared to
unaffected oral mucosa (P<0.001 and P=0.027, respectively). HER2 amplification in margin
tissue (P < 0.001) and swabs (P = 0.013), as well as the existence of three co-alterations in
margins and unaffected oral mucosa were correlated with shorter survival (P = 0.035 and
P=0.027, respectively).
Conclusion: HER2 amplification, as well as the presence of three co-alterations in margins and
unaffected oral mucosa proved to be markers of poor outcome in OSCC.
Abstract (sr)
Razviće malignih oboljenja uslovljeno je akumulacijom genetičkih i epigenetičkih
promena. Oralni skvamocelularni karcinom (OSCK) je najčešći malignitet usne duplje.
Patohistološkim metodama evaluacije rizika od pojave recidiva i metastaza nedostaje
senzitivnost, a taj problem može potencijalno da bude prevaziđen analizom molekularnih
promena u OSCK-u i njegovim marginama.
Ciljevi: (a) utvrditi prisustvo amplifikacije onkogena (c-MYC i HER2) i metilacije tumor
supresorskih gena (P14 i P16) u tumoru, margini i zdravoj oralnoj sluzokoži pacijenata sa
OSCK; (b) ustanoviti postojanje asocijacije između molekularnih i kliničkih parametara.
Materijal i metode. DNK je izolovana iz tkiva tumora, margina i oralne sluzokože 40 pacijenata
sa OSCK-om, operisanih na Klinici za maksilofacijalnu hirurgiju Stomatološkog fakulteta.
Prisustvo amplifikacije C-MYC i HER2 gena određeno je metodom PCR u realnom vremenu, a
P14 i P16 metilacije metodom metil-specifičnog PCR-a. Statistička analiza SPSS paketom je
primenjena za procenu asocijacije između molekularnih i kliničkih nalaza.
Rezultati: Najveća učestalost promena pokazana je u tumorskom tkivu, a najmanja u zdravoj
oralnoj sluzokoži. Višestruke promene (ko-alteracije) su bile znatno češće u tumorima i
tumorskim marginama nego u sluzokoži (P <0.001 odnosno P = 0.027). Amplifikacija HER2
gena u tkivu margina (P <0.001) i sluzokoži (P = 0.013), kao i postojanje tri ko-alteracije u
marginama i neizmenjenoj oralnoj sluzokoži korelisane su sa kraćim preživljavanjem (P = 0.035
odnsono P = 0.027).
Zaključak: HER2 amplifikacija, kao i prisustvo tri ko-alteracije u marginama i zdravoj oralnoj
sluzokoži pokazale su se kao prediktori lošeg ishoda u OSCK-u.
Authors Key words
amplification, methylation, oncogenes, HER2, c-MYC, tumor suppressor genes,
tumors, tumor margins, healthy mucosa, oral cancer
Authors Key words
amplifikacija, metilacija, onkogeni, HER2, c-MYC, tumor supresorski geni,
tumori, tumorske margine, zdrava sluzokoža, kancer usne duplje
Classification
616.31-006.6:577.2(043.3)
Type
Tekst
Abstract (en)
The development of malignant diseases is due to the accumulation of genetic and
epigenetic changes. Oral squamous cell carcinoma (OSCC) is an aggressive and very common
malignancy of the oral cavity. Patho-histological methods lack sensitivity in terms of the
evaluation of the risk of OSCC recurrence and metastases. This issue can potentially be
overcome by assessing molecular changes in OSCC and its margins.
Aims: (a) to determine the presence of oncogene amplification (c-MYC and HER2) and tumor
suppressor gene methylation (P14 and P16) in tumor, tumor margin and healthy oral mucosa of
patients with OSCC; (b) establish a potential association between molecular and clinical
parameters.
Material and methods: DNA was isolated from tumor, margin and oral mucosa tissue of 40
patients with OSCC, operated at the Clinic for Maxillofacial Surgery, School of Dental
Medicine. The presence of C-MYC and HER2 gene amplification was determined by real-time
PCR, and P14 and P16 methylation by methyl-specific PCR. Statistical analysis with SPSS was
applied to estimate the association between molecular and clinical findings.
Results: Tumor tissues showed the highest prevalence of alterations and oral mucosa the lowest.
Multiple alterations were significantly more frequent in tumors and tumor margins compared to
unaffected oral mucosa (P<0.001 and P=0.027, respectively). HER2 amplification in margin
tissue (P < 0.001) and swabs (P = 0.013), as well as the existence of three co-alterations in
margins and unaffected oral mucosa were correlated with shorter survival (P = 0.035 and
P=0.027, respectively).
Conclusion: HER2 amplification, as well as the presence of three co-alterations in margins and
unaffected oral mucosa proved to be markers of poor outcome in OSCC.
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