Somatic Mutations Alter Interleukin Signaling Pathways in Grade II Invasive Breast Cancer Patients: An Egyptian Experience
This study aimed to investigate the impact of somatic mutations on various interleukin signaling pathways associated with grade II invasive breast cancer (BC) in Egyptian patients to broaden our understanding of their role in promoting carcinogenesis. Fifty-five grade II invasive BC patients were in...
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2022-11-01
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author | Auhood Nassar Abdel Rahman N. Zekri Mostafa H. Elberry Ahmed M. Lymona Mai M. Lotfy Mohamed Abouelhoda Amira Salah El-Din Youssef |
author_facet | Auhood Nassar Abdel Rahman N. Zekri Mostafa H. Elberry Ahmed M. Lymona Mai M. Lotfy Mohamed Abouelhoda Amira Salah El-Din Youssef |
author_sort | Auhood Nassar |
collection | DOAJ |
description | This study aimed to investigate the impact of somatic mutations on various interleukin signaling pathways associated with grade II invasive breast cancer (BC) in Egyptian patients to broaden our understanding of their role in promoting carcinogenesis. Fifty-five grade II invasive BC patients were included in this study. Data for somatic mutations in 45 BC patients were already available from a previous study. Data for somatic mutations of 10 new BC patients were included in the current study. Somatic mutations were identified using targeted next-generation sequencing (NGS) to study their involvement in interleukin signaling pathways. For pathway analysis, we used ingenuity variant analysis (IVA) to identify the most significantly altered pathways. We identified somatic mutations in components of the interleukin-2, interleukin-6, and inter-leukin-7 signaling pathways, including mutations in <i>JAK1, JAK2, JAK3, SOCS1, IL7R, MCL1, BCL2, MTOR</i>, and <i>IL6ST</i> genes. Interestingly, six mutations which were likely to be novel deleterious were identified: two in the <i>SCH1</i> gene, two in the <i>IL2</i> gene, and one in each of the <i>IL7R</i> and <i>JUN</i> genes. According to IVA analysis, interleukin 2, interleukin 6, and interleukin 7 signaling pathways were the most altered in 34.5%, 29%, and 23.6% of our BC group, respectively. Our multigene panel sequencing analysis reveals that our BC patients have altered interleukin signaling pathways. So, these results highlight the prominent role of interleukins in the carcinogenesis process and suggest its potential role as promising candidates for personalized therapy in Egyptian patients. |
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spelling | doaj.art-49c06e94543a48b7bed8ebe55195f6702023-11-24T14:03:25ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-11-0144125890590110.3390/cimb44120401Somatic Mutations Alter Interleukin Signaling Pathways in Grade II Invasive Breast Cancer Patients: An Egyptian ExperienceAuhood Nassar0Abdel Rahman N. Zekri1Mostafa H. Elberry2Ahmed M. Lymona3Mai M. Lotfy4Mohamed Abouelhoda5Amira Salah El-Din Youssef6Cancer Biology Department, Virology and Immunology Unit, National Cancer Institute, Cairo University, Cairo 11796, EgyptCancer Biology Department, Virology and Immunology Unit, National Cancer Institute, Cairo University, Cairo 11796, EgyptCancer Biology Department, Virology and Immunology Unit, National Cancer Institute, Cairo University, Cairo 11796, EgyptSurgical Oncology Department, National Cancer Institute, Cairo University, Cairo 11796, EgyptCancer Biology Department, Virology and Immunology Unit, National Cancer Institute, Cairo University, Cairo 11796, EgyptFaculty of Engineering, Cairo University, Cairo 12613, EgyptCancer Biology Department, Virology and Immunology Unit, National Cancer Institute, Cairo University, Cairo 11796, EgyptThis study aimed to investigate the impact of somatic mutations on various interleukin signaling pathways associated with grade II invasive breast cancer (BC) in Egyptian patients to broaden our understanding of their role in promoting carcinogenesis. Fifty-five grade II invasive BC patients were included in this study. Data for somatic mutations in 45 BC patients were already available from a previous study. Data for somatic mutations of 10 new BC patients were included in the current study. Somatic mutations were identified using targeted next-generation sequencing (NGS) to study their involvement in interleukin signaling pathways. For pathway analysis, we used ingenuity variant analysis (IVA) to identify the most significantly altered pathways. We identified somatic mutations in components of the interleukin-2, interleukin-6, and inter-leukin-7 signaling pathways, including mutations in <i>JAK1, JAK2, JAK3, SOCS1, IL7R, MCL1, BCL2, MTOR</i>, and <i>IL6ST</i> genes. Interestingly, six mutations which were likely to be novel deleterious were identified: two in the <i>SCH1</i> gene, two in the <i>IL2</i> gene, and one in each of the <i>IL7R</i> and <i>JUN</i> genes. According to IVA analysis, interleukin 2, interleukin 6, and interleukin 7 signaling pathways were the most altered in 34.5%, 29%, and 23.6% of our BC group, respectively. Our multigene panel sequencing analysis reveals that our BC patients have altered interleukin signaling pathways. So, these results highlight the prominent role of interleukins in the carcinogenesis process and suggest its potential role as promising candidates for personalized therapy in Egyptian patients.https://www.mdpi.com/1467-3045/44/12/401multigene sequencingbreast cancerEgyptiansomatic mutationsNGSinterleukin signaling pathways |
spellingShingle | Auhood Nassar Abdel Rahman N. Zekri Mostafa H. Elberry Ahmed M. Lymona Mai M. Lotfy Mohamed Abouelhoda Amira Salah El-Din Youssef Somatic Mutations Alter Interleukin Signaling Pathways in Grade II Invasive Breast Cancer Patients: An Egyptian Experience Current Issues in Molecular Biology multigene sequencing breast cancer Egyptian somatic mutations NGS interleukin signaling pathways |
title | Somatic Mutations Alter Interleukin Signaling Pathways in Grade II Invasive Breast Cancer Patients: An Egyptian Experience |
title_full | Somatic Mutations Alter Interleukin Signaling Pathways in Grade II Invasive Breast Cancer Patients: An Egyptian Experience |
title_fullStr | Somatic Mutations Alter Interleukin Signaling Pathways in Grade II Invasive Breast Cancer Patients: An Egyptian Experience |
title_full_unstemmed | Somatic Mutations Alter Interleukin Signaling Pathways in Grade II Invasive Breast Cancer Patients: An Egyptian Experience |
title_short | Somatic Mutations Alter Interleukin Signaling Pathways in Grade II Invasive Breast Cancer Patients: An Egyptian Experience |
title_sort | somatic mutations alter interleukin signaling pathways in grade ii invasive breast cancer patients an egyptian experience |
topic | multigene sequencing breast cancer Egyptian somatic mutations NGS interleukin signaling pathways |
url | https://www.mdpi.com/1467-3045/44/12/401 |
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