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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	202
Number of pages	19
Journal	BMC Medical Genomics
Volume	17
Issue number	1
DOIs	https://doi.org/10.1186/s12920-024-01965-w
Publication status	Published - 9 Aug 2024

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Living Donor Liver Transplantation (LDLT)
Hepatocelleular carcinoma (HCC)
Whole exome sequencing
Mutational signature

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Correction: Genomic landscape of hepatocellular carcinoma in Egyptian patients by whole exome sequencing
Kassem, P. H., Montasser, I. F., Mahmoud, M. R., Ghorab, R. A., AbdelHakam, D. A., Fathi, M. E. S. A., Wahed, M. A. A., Mohey, K., Ibrahim, M., El Hadidi, M., Masssoud, Y. M., Salah, M., Abugable, A., Bahaa, M., Khamisy, S. E. & Meteini, M. E., 12 Nov 2024, (E-pub ahead of print) In: BMC Medical Genomics. 17, 1, 268.
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Kassem, P. H., Montasser, I. F., Mahmoud, R. M., Ghorab, R. A., AbdelHakam, D. A., Fathi, M. EL. S. A., Wahed, M. A. A., Mohey, K., Ibrahim, M., Hadidi, M. E., Masssoud, Y. M., Salah, M., Abugable, A., Bahaa, M., Khamisy, S. E., & Meteini, M. E. (2024). Genomic landscape of hepatocellular carcinoma in Egyptian patients by whole exome sequencing. BMC Medical Genomics, 17(1), Article 202. https://doi.org/10.1186/s12920-024-01965-w

@article{7b368a5bb75242b5a7454b64a4e61d23,

title = "Genomic landscape of hepatocellular carcinoma in Egyptian patients by whole exome sequencing",

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 = "Living Donor Liver Transplantation (LDLT), Hepatocelleular carcinoma (HCC), Whole exome sequencing, Mutational signature",

author = "Kassem, \{Perihan Hamdy\} and Montasser, \{Iman Fawzy\} and Mahmoud, \{Ramy Mohamed\} and Ghorab, \{Rasha Ahmed\} and AbdelHakam, \{Dina A.\} and Fathi, \{Marium EL Sayed Ahmad\} and Wahed, \{Marwa A. Abdel\} and Khaled Mohey and Mariam Ibrahim and Hadidi, \{Mohamed El\} and Masssoud, \{Yasmine M.\} and Manar Salah and Arwa Abugable and Mohamad Bahaa and Khamisy, \{Sherif El\} and Meteini, \{Mahmoud El\}",

year = "2024",

month = aug,

day = "9",

doi = "10.1186/s12920-024-01965-w",

language = "English",

volume = "17",

journal = "BMC Medical Genomics",

issn = "1755-8794",

publisher = "BioMed Central",

number = "1",

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Kassem, PH, Montasser, IF, Mahmoud, RM, Ghorab, RA, AbdelHakam, DA, Fathi, MELSA, Wahed, MAA, Mohey, K, Ibrahim, M, Hadidi, ME, Masssoud, YM, Salah, M, Abugable, A, Bahaa, M, Khamisy, SE & Meteini, ME 2024, 'Genomic landscape of hepatocellular carcinoma in Egyptian patients by whole exome sequencing', BMC Medical Genomics, vol. 17, no. 1, 202. https://doi.org/10.1186/s12920-024-01965-w

TY - JOUR

T1 - Genomic landscape of hepatocellular carcinoma in Egyptian patients by whole exome sequencing

AU - Kassem, Perihan Hamdy

AU - Montasser, Iman Fawzy

AU - Mahmoud, Ramy Mohamed

AU - Ghorab, Rasha Ahmed

AU - AbdelHakam, Dina A.

AU - Fathi, Marium EL Sayed Ahmad

AU - Wahed, Marwa A. Abdel

AU - Mohey, Khaled

AU - Ibrahim, Mariam

AU - Hadidi, Mohamed El

AU - Masssoud, Yasmine M.

AU - Salah, Manar

AU - Abugable, Arwa

AU - Bahaa, Mohamad

AU - Khamisy, Sherif El

AU - Meteini, Mahmoud El

PY - 2024/8/9

Y1 - 2024/8/9

N2 - 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.

AB - 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.

KW - Living Donor Liver Transplantation (LDLT)

KW - Hepatocelleular carcinoma (HCC)

KW - Whole exome sequencing

KW - Mutational signature

U2 - 10.1186/s12920-024-01965-w

DO - 10.1186/s12920-024-01965-w

M3 - Article

SN - 1755-8794

VL - 17

JO - BMC Medical Genomics

JF - BMC Medical Genomics

IS - 1

M1 - 202

ER -

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

Abstract

UN SDGs

Keywords

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

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