TY - JOUR

T1 - Germline variants in proto-oncogenes and tumor suppressor 2 genes in women with cervical cancer

AU - Хуснутдинова, Эльза Камилевна

AU - Khusainova, Rita

AU - Lenkova, Kseniya

AU - Minyazeva, R.,

AU - Zaripova, Aliya

AU - Гилязова, Ирина Ришатовна

AU - Mokrysheva, N.; ,

AU - Minniakhmetov, Ildar

PY - 2024/10/25

Y1 - 2024/10/25

N2 - BACKGROUND/OBJECTIVES: Cervical cancer (CC) remains a significant global health challenge, characterized by genetic heterogeneity and a complex molecular landscape, both of which contribute to its pathogenesis. This study aimed to investigate germline variants in proto-oncogenes and tumor suppressor genes in cervical cancer patients, with the objective of clarifying their potential role in disease development.METHODS: We utilized a custom next-generation sequencing (NGS) panel targeting 48 genes implicated in oncogenesis. Germline DNA samples from cervical cancer patients were analyzed in order to identify nucleotide sequence alterations. Variants were classified according to pathogenicity and clinical relevance, based on established guidelines.RESULTS: A total of 148 nucleotide variants were detected within the cohort. Of these, 35 variants (23.6%) were classified as benign. In contrast, 105 variants (70.9%) were identified as variants of uncertain significance (VUSs). Moreover, seven pathogenic or likely pathogenic mutations were discovered, along with the polymorphic variant rs1042522 in the TP53 gene, which has been associated with an increased risk of cervical cancer. CONCLUSIONS: Our findings contribute to expanding our understanding of the molecular genetic landscape of cervical cancer. They emphasize the potential contribution of rare germline mutations to its development and progression. These results highlight the importance of comprehensive genetic screening in order to improve diagnostic and therapeutic approaches for cervical cancer patients.

AB - BACKGROUND/OBJECTIVES: Cervical cancer (CC) remains a significant global health challenge, characterized by genetic heterogeneity and a complex molecular landscape, both of which contribute to its pathogenesis. This study aimed to investigate germline variants in proto-oncogenes and tumor suppressor genes in cervical cancer patients, with the objective of clarifying their potential role in disease development.METHODS: We utilized a custom next-generation sequencing (NGS) panel targeting 48 genes implicated in oncogenesis. Germline DNA samples from cervical cancer patients were analyzed in order to identify nucleotide sequence alterations. Variants were classified according to pathogenicity and clinical relevance, based on established guidelines.RESULTS: A total of 148 nucleotide variants were detected within the cohort. Of these, 35 variants (23.6%) were classified as benign. In contrast, 105 variants (70.9%) were identified as variants of uncertain significance (VUSs). Moreover, seven pathogenic or likely pathogenic mutations were discovered, along with the polymorphic variant rs1042522 in the TP53 gene, which has been associated with an increased risk of cervical cancer. CONCLUSIONS: Our findings contribute to expanding our understanding of the molecular genetic landscape of cervical cancer. They emphasize the potential contribution of rare germline mutations to its development and progression. These results highlight the importance of comprehensive genetic screening in order to improve diagnostic and therapeutic approaches for cervical cancer patients.

KW - cancer

KW - molecular genetic landscape

KW - oncogenes

KW - tumor suppressor genes

UR - https://www.mendeley.com/catalogue/8d6a1bea-a96f-3b7a-8096-7b8ddd8e88a1/

U2 - 10.3390/biomedicines12112454

DO - 10.3390/biomedicines12112454

M3 - Article

C2 - 39595021

VL - 12

JO - Biomedicines

JF - Biomedicines

SN - 2227-9059

IS - 11

M1 - 2454

ER -