Mutational profiles of marker genes of cervical carcinoma in Bangladeshi patients.
Adult
Antineoplastic Agents
/ pharmacology
Bangladesh
Biomarkers, Tumor
/ antagonists & inhibitors
Cervix Uteri
/ pathology
Chemotherapy, Adjuvant
/ methods
Class I Phosphatidylinositol 3-Kinases
/ genetics
Clinical Decision-Making
Computer Simulation
DNA Mutational Analysis
Decision Support Techniques
ErbB Receptors
/ genetics
Female
Humans
Hysterectomy
Middle Aged
Molecular Targeted Therapy
/ methods
Mutation
Proto-Oncogene Proteins p21(ras)
/ genetics
Uterine Cervical Neoplasms
/ genetics
Cervical cancer
EGFR
HPV
KRAS
Mutation
PIK3CA
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
18 Mar 2021
18 Mar 2021
Historique:
received:
24
06
2020
accepted:
12
02
2021
entrez:
19
3
2021
pubmed:
20
3
2021
medline:
4
5
2021
Statut:
epublish
Résumé
Cervical cancer is a gynecologic cancer type that develops in the cervix, accounting for 8% mortality of all female cancer patients. Infection with specific human papillomavirus (HPV) types is considered the most severe risk factor for cervical cancer. In the context of our socioeconomic conditions, an increasing burden of this disease and high mortality rate prevail in Bangladesh. Although several researches related to the epidemiology, HPV vaccination, and treatment modalities were conducted, researches on the mutation profiles of marker genes in cervical cancer in Bangladesh remain unexplored. In this study, five different genomic regions within the top three most frequently mutated genes (EGFR, KRAS and PIK3CA) in COSMIC database with a key role in the development of cervical cancers were selected to study the mutation frequency in Bangladeshi patients. In silico analysis was done in two steps: nucleotide sequence analysis and its corresponding amino acid analysis. DNA from 46 cervical cancer tissue samples were extracted and amplified by PCR, using 1 set of primers designed for EGFR and 2 sets of primers designed for two different regions of both PIK3CA and KRAS gene. In total, 39 mutations were found in 26 patient samples. Eleven different mutations (23.91%), twenty-four different mutations (52.17%) and four mutations (8.7%) were found in amplified EGFR, PIK3CA and KRAS gene fragments, respectively; among which 1 (EGFR) was common in seven patient samples and 2 (PIKCA) were found in more than 1 patient. Our study shows that except for KRAS, the frequency of observed mutations in our patients is higher than those reported earlier in other parts of the world. Most of the exonic mutations were found only in the PIK3CA and EGFR genes. The study can be used as a basis to build a mutation database for cervical cancer in Bangladesh with the possibility of targetable oncogenic mutations. Further explorations are needed to establish future diagnostics, personalized medicine decisions, and other pharmaceutical applications for specific cancer subtypes.
Sections du résumé
BACKGROUND
BACKGROUND
Cervical cancer is a gynecologic cancer type that develops in the cervix, accounting for 8% mortality of all female cancer patients. Infection with specific human papillomavirus (HPV) types is considered the most severe risk factor for cervical cancer. In the context of our socioeconomic conditions, an increasing burden of this disease and high mortality rate prevail in Bangladesh. Although several researches related to the epidemiology, HPV vaccination, and treatment modalities were conducted, researches on the mutation profiles of marker genes in cervical cancer in Bangladesh remain unexplored.
METHODS
METHODS
In this study, five different genomic regions within the top three most frequently mutated genes (EGFR, KRAS and PIK3CA) in COSMIC database with a key role in the development of cervical cancers were selected to study the mutation frequency in Bangladeshi patients. In silico analysis was done in two steps: nucleotide sequence analysis and its corresponding amino acid analysis.
RESULTS
RESULTS
DNA from 46 cervical cancer tissue samples were extracted and amplified by PCR, using 1 set of primers designed for EGFR and 2 sets of primers designed for two different regions of both PIK3CA and KRAS gene. In total, 39 mutations were found in 26 patient samples. Eleven different mutations (23.91%), twenty-four different mutations (52.17%) and four mutations (8.7%) were found in amplified EGFR, PIK3CA and KRAS gene fragments, respectively; among which 1 (EGFR) was common in seven patient samples and 2 (PIKCA) were found in more than 1 patient. Our study shows that except for KRAS, the frequency of observed mutations in our patients is higher than those reported earlier in other parts of the world. Most of the exonic mutations were found only in the PIK3CA and EGFR genes.
CONCLUSIONS
CONCLUSIONS
The study can be used as a basis to build a mutation database for cervical cancer in Bangladesh with the possibility of targetable oncogenic mutations. Further explorations are needed to establish future diagnostics, personalized medicine decisions, and other pharmaceutical applications for specific cancer subtypes.
Identifiants
pubmed: 33736612
doi: 10.1186/s12885-021-07906-5
pii: 10.1186/s12885-021-07906-5
pmc: PMC7977314
doi:
Substances chimiques
Antineoplastic Agents
0
Biomarkers, Tumor
0
KRAS protein, human
0
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
289Références
Lancet Glob Health. 2016 Sep;4(9):e609-16
pubmed: 27470177
Nucleic Acids Res. 2019 Jan 8;47(D1):D941-D947
pubmed: 30371878
Cancer. 2013 Nov 1;119(21):3776-83
pubmed: 24037752
Genome Biol. 2016 Jun 06;17(1):122
pubmed: 27268795
Science. 1982 Sep 3;217(4563):937-9
pubmed: 6287573
Int J Radiat Oncol Biol Phys. 2004;59(2 Suppl):21-6
pubmed: 15142631
Nature. 2017 Mar 16;543(7645):378-384
pubmed: 28112728
Bioinformatics. 2017 Feb 15;33(4):471-474
pubmed: 27563026
J Virol. 2019 Jan 4;93(2):
pubmed: 30333178
Int J Gynecol Cancer. 2008 Jul-Aug;18(4):749-54
pubmed: 17949425
Br J Cancer. 2011 Jul 26;105(3):420-7
pubmed: 21730982
J Gynecol Oncol. 2018 Jan;29(1):e4
pubmed: 29185262
Nat Methods. 2010 Apr;7(4):248-9
pubmed: 20354512
N Engl J Med. 2008 Jan 31;358(5):502-11
pubmed: 18234754
J Natl Cancer Inst. 1995 Jun 7;87(11):796-802
pubmed: 7791229
J Mol Biol. 1990 Oct 5;215(3):403-10
pubmed: 2231712
Nat Protoc. 2009;4(7):1073-81
pubmed: 19561590
Gynecol Oncol. 2013 Mar;128(3):409-14
pubmed: 23266353
Cancer Med. 2012 Aug;1(1):59-67
pubmed: 23342254
Annu Rev Microbiol. 1994;48:427-47
pubmed: 7826013
J Clin Pathol. 2002 Apr;55(4):244-65
pubmed: 11919208
Nucleic Acids Res. 2005 Jan 1;33(Database issue):D34-8
pubmed: 15608212
Sci Rep. 2015 Sep 11;5:14035
pubmed: 26358014
PLoS One. 2015 Jul 21;10(7):e0133670
pubmed: 26197069
Am Fam Physician. 2000 Mar 1;61(5):1369-76
pubmed: 10735343
Science. 1993 Nov 26;262(5138):1444-8
pubmed: 8248783
Clin Cancer Res. 2015 Jun 1;21(11):2530-7
pubmed: 25724520
PLoS One. 2013 Aug 09;8(8):e71711
pubmed: 23951226
J Pathol. 2006 Jan;208(2):152-64
pubmed: 16362994
Proteins. 2006 Mar 1;62(4):1125-32
pubmed: 16372356
J Gen Virol. 1995 Apr;76 ( Pt 4):1057-62
pubmed: 9049358
J Pathol. 1999 Sep;189(1):12-9
pubmed: 10451482