Genomic landscape of hepatocellular carcinoma in Egyptian patients by whole exome sequencing

Perihan Hamdy Kassem; Iman Fawzy Montasser; Ramy Mohamed Mahmoud; Rasha Ahmed Ghorab; Dina A AbdelHakam; Marium El Sayed Ahmad Fathi; Marwa A Abdel Wahed; Khaled Mohey; Mariam Ibrahim; Mohamed El Hadidi; Yasmine M Masssoud; Manar Salah; Arwa Abugable; Mohamad Bahaa; Sherif El Khamisy; Mahmoud El Meteini

doi:10.1186/s12920-024-01965-w

Genomic landscape of hepatocellular carcinoma in Egyptian patients by whole exome sequencing

BMC Med Genomics. 2024 Aug 9;17(1):202. doi: 10.1186/s12920-024-01965-w.

Authors

Perihan Hamdy Kassem¹, Iman Fawzy Montasser², Ramy Mohamed Mahmoud¹, Rasha Ahmed Ghorab¹, Dina A AbdelHakam¹, Marium El Sayed Ahmad Fathi¹, Marwa A Abdel Wahed¹, Khaled Mohey¹, Mariam Ibrahim³, Mohamed El Hadidi^{4

5}, Yasmine M Masssoud⁶, Manar Salah⁶, Arwa Abugable⁷, Mohamad Bahaa⁸, Sherif El Khamisy⁷, Mahmoud El Meteini⁸

Affiliations

¹ Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
² Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. imanfawzy2@gmail.com.
³ Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
⁴ Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham Dubai Campus, Dubai, United Arab Emirates.
⁵ Bioinformatics Group, Center for Informatics Science(CIS), School of Information Technology and Computer Science(ITCS), Nile University, Giza, Egypt.
⁶ Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
⁷ School of Biosciences, University of Sheffield, Sheffield, UK.
⁸ Hepato-Pancreatico-Biliary Surgery Department and liver Transplantation, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Chronic hepatitis and liver cirrhosis lead to accumulation of genetic alterations driving HCC pathogenesis. This study is designed to explore genomic landscape of HCC in Egyptian patients by whole exome sequencing.

Methods: Whole exome sequencing using Ion Torrent was done on 13 HCC patients, who underwent surgical intervention (7 patients underwent living donor liver transplantation (LDLT) and 6 patients had surgical resection}.

Results: Mutational signature was mostly S1, S5, S6, and S12 in HCC. Analysis of highly mutated genes in both HCC and Non-HCC revealed the presence of highly mutated genes in HCC (AHNAK2, MUC6, MUC16, TTN, ZNF17, FLG, MUC12, OBSCN, PDE4DIP, MUC5b, and HYDIN). Among the 26 significantly mutated HCC genes-identified across 10 genome sequencing studies-in addition to TCGA, APOB and RP1L1 showed the highest number of mutations in both HCC and Non-HCC tissues. Tier 1, Tier 2 variants in TCGA SMGs in HCC and Non-HCC (TP53, PIK3CA, CDKN2A, and BAP1). Cancer Genome Landscape analysis revealed Tier 1 and Tier 2 variants in HCC (MSH2) and in Non-HCC (KMT2D and ATM). For KEGG analysis, the significantly annotated clusters in HCC were Notch signaling, Wnt signaling, PI3K-AKT pathway, Hippo signaling, Apelin signaling, Hedgehog (Hh) signaling, and MAPK signaling, in addition to ECM-receptor interaction, focal adhesion, and calcium signaling. Tier 1 and Tier 2 variants KIT, KMT2D, NOTCH1, KMT2C, PIK3CA, KIT, SMARCA4, ATM, PTEN, MSH2, and PTCH1 were low frequency variants in both HCC and Non-HCC.

Conclusion: Our results are in accordance with previous studies in HCC regarding highly mutated genes, TCGA and specifically enriched pathways in HCC. Analysis for clinical interpretation of variants revealed the presence of Tier 1 and Tier 2 variants that represent potential clinically actionable targets. The use of sequencing techniques to detect structural variants and novel techniques as single cell sequencing together with multiomics transcriptomics, metagenomics will integrate the molecular pathogenesis of HCC in Egyptian patients.

Keywords: Hepatocelleular carcinoma (HCC); Living Donor Liver Transplantation (LDLT); Mutational signature; Whole exome sequencing.

MeSH terms

Adult
Carcinoma, Hepatocellular* / genetics
Carcinoma, Hepatocellular* / pathology
Egypt
Exome Sequencing*
Female
Genomics
Humans
Liver Neoplasms* / genetics
Liver Neoplasms* / pathology
Male
Middle Aged
Mutation*

Abstract

MeSH terms

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