Molecular cytogenetic analyses of hTERC (3q26) and MYC (8q24)
genes amplifications in correlation with oncogenic human
papillomavirus infection in Czech patients with cervical
intraepithelial neoplasia and cervical carcinomas

J 2015

Molecular cytogenetic analyses of hTERC (3q26) and MYC (8q24) genes amplifications in correlation with oncogenic human papillomavirus infection in Czech patients with cervical intraepithelial neoplasia and cervical carcinomas

KUGLÍK, Petr, Kateřina KAŠÍKOVÁ, Jan SMETANA, Vladimíra VALLOVÁ, Anna LAŠTŮVKOVÁ et. al.

Základní údaje

Originální název

Molecular cytogenetic analyses of hTERC (3q26) and MYC (8q24) genes amplifications in correlation with oncogenic human papillomavirus infection in Czech patients with cervical intraepithelial neoplasia and cervical carcinomas

Autoři

KUGLÍK, Petr (203 Česká republika, garant, domácí), Kateřina KAŠÍKOVÁ (203 Česká republika, domácí), Jan SMETANA (203 Česká republika, domácí), Vladimíra VALLOVÁ (703 Slovensko, domácí), Anna LAŠTŮVKOVÁ (203 Česká republika, domácí), Lucie MOUKOVÁ (203 Česká republika), Michaela CVANOVÁ (203 Česká republika, domácí) a Lucie BROŽOVÁ (203 Česká republika, domácí)

Vydání

Neoplasma, Slovenská akademie vied, 2015, 0028-2685

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

Genetika a molekulární biologie

Stát vydavatele

Slovensko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 1.961

Kód RIV

RIV/00216224:14310/15:00082235

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.4149/neo_2015_017

UT WoS

000362862300016

Klíčová slova anglicky

cervical cancer; cervical dysplasia; HPV infection; hTERC amplification; MYC amplification; FISH; array-CGH

Štítky

AKR, EL OK, podil, rivok

Změněno: 15. 12. 2015 10:51, RNDr. Michaela Cvanová, Ph.D.

Anotace

V originále

It is known that cervical cancer develop from precancerous intraepithelial neoplasia (CIN) which is characterized by series of genetic abnormalities. The progression of CIN to cervical carcinoma has been associated especially with the genomic integration of oncogenic human papilloma virus (HPV) and gain of the human telomerase RNA gene hTERC (3q26) and MYC (8q24). In this study, cytology specimens of cervical intraepithelial neoplasia and cervical carcinoma from 74 Czech women were analyzed using the triple-color Cervical FISH Probe Kit designed for identification of HPV infected cells and copy number aberration of the hTERC and MYC genes. HPV-positivity exhibited 70% of patients with premalignant lesions (CIN I - CIN III, carcinoma in situ), chromosomal changes were found in 53.3% of cases - MYC amplification had 33.3% of women with CIN I - CIN III and 50% with carcinoma in situ. Amplification of hTERC was detected in 16.7% of patient with CIN I, in 50% with CIN II, in 58.3% with CIN III and in 66.7% with carcinoma in situ. Based on HPV-positivity and the occurrence of chromosomal aberrations, patients were divided into high-, intermediate- and low-risk group. Among women with cervical carcinomas, HPV infection was detected in 90.1% of specimens and chromosomal aberrations were found in 87.5% of samples. Amplification of MYC gene was detected in 25% and hTERC gene in 62.5% of patients. According to the histopathological grade of tumors, MYC gene amplification occurred more frequently in specimens of spinocellular carcinoma than adenocarcinoma (p=0.029). We found no association between the frequency of cytogenetic lesions and the incidence of lymphangiogenesis or lymph node metastases in cervical carcinoma patients. Simultaneous hTERC and MYC genes amplification was significantly more frequent in samples of cervical carcinomas than in premalignant lesions (p=0.008).In a cohort of 26 patients with cervical carcinoma we used oligo-based GGH+SNP microarray technique for the high resolution mapping of copy number changes of hTERC and MYC genes. We found that recurrent gain of genetic material in chromosome 3q26 area carrying hTERC gene of size 43.6 Mb between 3q25.1-3qter and duplication of 3q were the most common genomic identifications of amplified gene. In MYC locus array-CGH profiling identified duplication of 8q and trisomy 8 as frequent genomic changes.Our work confirmed that in cervical carcinoma gains of hTERC and MYC genes are specific genomic changes associated with developing of malignant phenotype. We also showed that in premalignant stages HPV-FISH assay can be used as an effective diagnostic procedure to identify patients carrying highly risking HPV infection and chromosomal aberrations associated with this malignancy. KEYWORDS: cervical cancer, cervical dysplasia, HPV infection, hTERC amplification, MYC amplification, FISH, array-CGH.

Návaznosti

EE2.3.20.0183, projekt VaV

Název: Centrum experimentální biomedicíny

NT11089, projekt VaV

Název: Diagnostický význam amplifikace genů hTERC a MYCC při vzniku a vývoji cervikálních intraepiteliálních dysplázií a karcinomu děložního hrdla

Citovat

KUGLÍK, Petr, Kateřina KAŠÍKOVÁ, Jan SMETANA, Vladimíra VALLOVÁ, Anna LAŠTŮVKOVÁ, Lucie MOUKOVÁ, Michaela CVANOVÁ a Lucie BROŽOVÁ. Molecular cytogenetic analyses of hTERC (3q26) and MYC (8q24) genes amplifications in correlation with oncogenic human papillomavirus infection in Czech patients with cervical intraepithelial neoplasia and cervical carcinomas. Neoplasma. Slovenská akademie vied, 2015, roč. 62, č. 1, s. 130-139. ISSN 0028-2685. Dostupné z: https://dx.doi.org/10.4149/neo_2015_017.

@article{1216527,
   author = {Kuglík, Petr and Kašíková, Kateřina and Smetana, Jan and Vallová, Vladimíra and Laštůvková, Anna and Mouková, Lucie and Cvanová, Michaela and Brožová, Lucie},
   article_number = {1},
   doi = {http://dx.doi.org/10.4149/neo_2015_017},
   keywords = {cervical cancer; cervical dysplasia; HPV infection; hTERC amplification; MYC amplification; FISH; array-CGH},
   language = {eng},
   issn = {0028-2685},
   journal = {Neoplasma},
   title = {Molecular cytogenetic analyses of hTERC (3q26) and MYC (8q24) genes amplifications in correlation with oncogenic human papillomavirus infection in Czech patients with cervical intraepithelial neoplasia and cervical carcinomas},
   url = {http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=4041&category_id=117&option=com_virtuemar},
   volume = {62},
   year = {2015}
}

TY  - JOUR
ID  - 1216527
AU  - Kuglík, Petr - Kašíková, Kateřina - Smetana, Jan - Vallová, Vladimíra - Laštůvková, Anna - Mouková, Lucie - Cvanová, Michaela - Brožová, Lucie
PY  - 2015
TI  - Molecular cytogenetic analyses of hTERC (3q26) and MYC (8q24) genes amplifications in correlation with oncogenic human papillomavirus infection in Czech patients with cervical intraepithelial neoplasia and cervical carcinomas
JF  - Neoplasma
VL  - 62
IS  - 1
SP  - 130-139
EP  - 130-139
PB  - Slovenská akademie vied
SN  - 00282685
KW  - cervical cancer
KW  - cervical dysplasia
KW  - HPV infection
KW  - hTERC amplification
KW  - MYC amplification
KW  - FISH
KW  - array-CGH
UR  - http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=4041&category_id=117&option=com_virtuemar
N2  - It is known that cervical cancer develop from precancerous intraepithelial neoplasia (CIN) which is characterized by series of genetic abnormalities. The progression of CIN to cervical carcinoma has been associated especially with the genomic integration of oncogenic human papilloma virus (HPV) and gain of the human telomerase RNA gene hTERC (3q26) and MYC (8q24). In this study, cytology specimens of cervical intraepithelial neoplasia and cervical carcinoma from 74 Czech women were analyzed using the triple-color Cervical FISH Probe Kit designed for identification of HPV infected cells and copy number aberration of the hTERC and MYC genes. HPV-positivity exhibited 70% of patients with premalignant lesions (CIN I - CIN III, carcinoma in situ), chromosomal changes were found in 53.3% of cases - MYC amplification had 33.3% of women with CIN I - CIN III and 50% with carcinoma in situ. Amplification of hTERC was detected in 16.7% of patient with CIN I, in 50% with CIN II, in 58.3% with CIN III and in 66.7% with carcinoma in situ. Based on HPV-positivity and the occurrence of chromosomal aberrations, patients were divided into high-, intermediate- and low-risk group. Among women with cervical carcinomas, HPV infection was detected in 90.1% of specimens and chromosomal aberrations were found in 87.5% of samples. Amplification of MYC gene was detected in 25% and hTERC gene in 62.5% of patients. According to the histopathological grade of tumors, MYC gene amplification occurred more frequently in specimens of spinocellular carcinoma than adenocarcinoma (p=0.029). We found no association between the frequency of cytogenetic lesions and the incidence of lymphangiogenesis or lymph node metastases in cervical carcinoma patients. Simultaneous hTERC and MYC genes amplification was significantly more frequent in samples of cervical carcinomas than in premalignant lesions (p=0.008).In a cohort of 26 patients with cervical carcinoma we used oligo-based GGH+SNP microarray technique for the high resolution mapping of copy number changes of hTERC and MYC genes. We found that recurrent gain of genetic material in chromosome 3q26 area carrying hTERC gene of size 43.6 Mb between 3q25.1-3qter and duplication of 3q were the most common genomic identifications of amplified gene. In MYC locus array-CGH profiling identified duplication of 8q and trisomy 8 as frequent genomic changes.Our work confirmed that in cervical carcinoma gains of hTERC and MYC genes are specific genomic changes associated with developing of malignant phenotype. We also showed that in premalignant stages HPV-FISH assay can be used as an effective diagnostic procedure to identify patients carrying highly risking HPV infection and chromosomal aberrations associated with this malignancy. KEYWORDS: cervical cancer, cervical dysplasia, HPV infection, hTERC amplification, MYC amplification, FISH, array-CGH.
ER  -

KUGLÍK, Petr, Kateřina KAŠÍKOVÁ, Jan SMETANA, Vladimíra VALLOVÁ, Anna LAŠTŮVKOVÁ, Lucie MOUKOVÁ, Michaela CVANOVÁ a Lucie BROŽOVÁ. Molecular cytogenetic analyses of hTERC (3q26) and MYC (8q24) genes amplifications in correlation with oncogenic human papillomavirus infection in Czech patients with cervical intraepithelial neoplasia and cervical carcinomas. \textit{Neoplasma}. Slovenská akademie vied, 2015, roč.~62, č.~1, s.~130-139. ISSN~0028-2685. Dostupné z: https://dx.doi.org/10.4149/neo\_{}2015\_{}017.

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