Comprehensive genomic profiling reveals a unique genomic landscape in solid tumors in an Indian cancer cohort of 1000 patients: a single institutional experience

Abstract The use of Comprehensive Genomic Profiling (CGP) in clinical practice to detect broad-spectrum therapeutic, prognostic, and predictive biomarkers, including tumor mutational burden (TMB), microsatellite instability (MSI), somatic BRCA (sBRCA) and other homologous recombination repair genes...

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Main Authors: Mithua Ghosh, Sheela Mysore Lingaraju, Krishna C.R, Gautam Balaram, Ramya Kodandapani, Vijay E, Vijay K, Suhas N, Devika H, Shekar Patil, Satheesh Chiradoni Thungappa, Somorat Bhattacharjee, Sridhar P.S, Roshni Dasgupta, Mohammed Naseer, Srinivas B.J, Vishal Rao, Veena Ramaswamy, Radheshyam Naik, Govind Babu, Aarthi Ravichandran, Urvashi Bahadur, Krithika Murugan, Mahesh B, Lohith Reddy, Ajaikumar Basavalinga S
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Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-94762-z
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author Mithua Ghosh
Sheela Mysore Lingaraju
Krishna C.R
Gautam Balaram
Ramya Kodandapani
Vijay E
Vijay K
Suhas N
Devika H
Shekar Patil
Satheesh Chiradoni Thungappa
Somorat Bhattacharjee
Sridhar P.S
Roshni Dasgupta
Mohammed Naseer
Srinivas B.J
Vishal Rao
Veena Ramaswamy
Radheshyam Naik
Govind Babu
Aarthi Ravichandran
Urvashi Bahadur
Krithika Murugan
Mahesh B
Lohith Reddy
Ajaikumar Basavalinga S
author_facet Mithua Ghosh
Sheela Mysore Lingaraju
Krishna C.R
Gautam Balaram
Ramya Kodandapani
Vijay E
Vijay K
Suhas N
Devika H
Shekar Patil
Satheesh Chiradoni Thungappa
Somorat Bhattacharjee
Sridhar P.S
Roshni Dasgupta
Mohammed Naseer
Srinivas B.J
Vishal Rao
Veena Ramaswamy
Radheshyam Naik
Govind Babu
Aarthi Ravichandran
Urvashi Bahadur
Krithika Murugan
Mahesh B
Lohith Reddy
Ajaikumar Basavalinga S
author_sort Mithua Ghosh
collection DOAJ
description Abstract The use of Comprehensive Genomic Profiling (CGP) in clinical practice to detect broad-spectrum therapeutic, prognostic, and predictive biomarkers, including tumor mutational burden (TMB), microsatellite instability (MSI), somatic BRCA (sBRCA) and other homologous recombination repair genes (HRRs) provides a more cost-efficient and tissue-preserving approach than serial single-biomarker analysis. A total of 1000 biopsy-proven cancer patients at the HCG cancer center were profiled in an IRB-approved prospective study. The findings were discussed in the multidisciplinary molecular tumor board (MTB), and recommendations were documented in electronic medical records (EMRs) for clinical management and follow-up. A total of 1747 genomic alterations were detected (mean 1.7 mutations/sample), with 80% of patients having genetic alterations with therapeutic and prognostic implications (Tier I-32%, Tier II-50%). CGP revealed a greater number of druggable genes (47%) than did small panels (14%). Tumor-agnostic markers for immunotherapy (IO) were observed in 16% of the current cohort, based on which IO was initiated. In 13.5% of the cohort, alterations in the HRR pathway including sBRCA (5.5%) were detected providing an option for treatment with platinum or PARP inhibitors. Other significant alterations included those in EGFR, KRAS/BRAF, PIK3CA, cKIT, PDGFRA, ARID1A, ARID2, and FGFR. RNA sequencing revealed 55 + RNA alterations, including those in TMPRSS-ERG, RPS6KB1-VMP1, EML4-ALK, NTRK, PDGFRA and EWSR. Clinical outcome data were available via EMR for 618 patients (62%), out of whom 419 patients had druggable mutations (67%; 95% CI 88.9–93.9%) and 39 patients had 1 or more mutations with prognostic implications. However, only 200 patients (44%; 95% CI 39.1–48.1%) were included in the MTB discussion. Based on genomics reports, the treatment regimen was changed for 137 and 61 patients with and without clinical inputs from the MTB, respectively. The overall change in therapy based on CGP in the clinical cohort was 43%, which was greater in patients enrolled for MTB than in patients who had not undergone MTB. At the interim analysis, with a median follow-up of 18 months (range 12–24 months) after the change in therapy as per genomics report, 97 patients (71%) were found to be alive thus establishing the importance of CGP and MTB in personalized genomics-driven treatment.
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spelling doaj-art-c2571d7cfb484ca1aef66bdbaa9bbfd02025-08-20T03:06:49ZengNature PortfolioScientific Reports2045-23222025-04-0115111710.1038/s41598-025-94762-zComprehensive genomic profiling reveals a unique genomic landscape in solid tumors in an Indian cancer cohort of 1000 patients: a single institutional experienceMithua Ghosh0Sheela Mysore Lingaraju1Krishna C.R2Gautam Balaram3Ramya Kodandapani4Vijay E5Vijay K6Suhas N7Devika H8Shekar Patil9Satheesh Chiradoni Thungappa10Somorat Bhattacharjee11Sridhar P.S12Roshni Dasgupta13Mohammed Naseer14Srinivas B.J15Vishal Rao16Veena Ramaswamy17Radheshyam Naik18Govind Babu19Aarthi Ravichandran20Urvashi Bahadur21Krithika Murugan22Mahesh B23Lohith Reddy24Ajaikumar Basavalinga S25Triesta Sciences, A Unit of HeathCare Global Enterprises LimitedTriesta Sciences, A Unit of HeathCare Global Enterprises LimitedTriesta Sciences, A Unit of HeathCare Global Enterprises LimitedTriesta Sciences, A Unit of HeathCare Global Enterprises LimitedTriesta Sciences, A Unit of HeathCare Global Enterprises LimitedTriesta Sciences, A Unit of HeathCare Global Enterprises LimitedTriesta Sciences, A Unit of HeathCare Global Enterprises LimitedTriesta Sciences, A Unit of HeathCare Global Enterprises LimitedTriesta Sciences, A Unit of HeathCare Global Enterprises LimitedHealthCare Global Enterprises LimitedHealthCare Global Enterprises LimitedHealthCare Global Enterprises LimitedHealthCare Global Enterprises LimitedHealthCare Global Enterprises LimitedHealthCare Global Enterprises LimitedHealthCare Global Enterprises LimitedHealthCare Global Enterprises LimitedTriesta Sciences, A Unit of HeathCare Global Enterprises LimitedHealthCare Global Enterprises LimitedHealthCare Global Enterprises LimitedStrand Life SciencesStrand Life SciencesHealthCare Global Enterprises LimitedHealthCare Global Enterprises LimitedHealthCare Global Enterprises LimitedHealthCare Global Enterprises LimitedAbstract The use of Comprehensive Genomic Profiling (CGP) in clinical practice to detect broad-spectrum therapeutic, prognostic, and predictive biomarkers, including tumor mutational burden (TMB), microsatellite instability (MSI), somatic BRCA (sBRCA) and other homologous recombination repair genes (HRRs) provides a more cost-efficient and tissue-preserving approach than serial single-biomarker analysis. A total of 1000 biopsy-proven cancer patients at the HCG cancer center were profiled in an IRB-approved prospective study. The findings were discussed in the multidisciplinary molecular tumor board (MTB), and recommendations were documented in electronic medical records (EMRs) for clinical management and follow-up. A total of 1747 genomic alterations were detected (mean 1.7 mutations/sample), with 80% of patients having genetic alterations with therapeutic and prognostic implications (Tier I-32%, Tier II-50%). CGP revealed a greater number of druggable genes (47%) than did small panels (14%). Tumor-agnostic markers for immunotherapy (IO) were observed in 16% of the current cohort, based on which IO was initiated. In 13.5% of the cohort, alterations in the HRR pathway including sBRCA (5.5%) were detected providing an option for treatment with platinum or PARP inhibitors. Other significant alterations included those in EGFR, KRAS/BRAF, PIK3CA, cKIT, PDGFRA, ARID1A, ARID2, and FGFR. RNA sequencing revealed 55 + RNA alterations, including those in TMPRSS-ERG, RPS6KB1-VMP1, EML4-ALK, NTRK, PDGFRA and EWSR. Clinical outcome data were available via EMR for 618 patients (62%), out of whom 419 patients had druggable mutations (67%; 95% CI 88.9–93.9%) and 39 patients had 1 or more mutations with prognostic implications. However, only 200 patients (44%; 95% CI 39.1–48.1%) were included in the MTB discussion. Based on genomics reports, the treatment regimen was changed for 137 and 61 patients with and without clinical inputs from the MTB, respectively. The overall change in therapy based on CGP in the clinical cohort was 43%, which was greater in patients enrolled for MTB than in patients who had not undergone MTB. At the interim analysis, with a median follow-up of 18 months (range 12–24 months) after the change in therapy as per genomics report, 97 patients (71%) were found to be alive thus establishing the importance of CGP and MTB in personalized genomics-driven treatment.https://doi.org/10.1038/s41598-025-94762-zComprehensive genomic profilingNext-generation sequencingPrecision oncologyTargeted therapyImmunotherapyMultidisciplinary molecular tumor board
spellingShingle Mithua Ghosh
Sheela Mysore Lingaraju
Krishna C.R
Gautam Balaram
Ramya Kodandapani
Vijay E
Vijay K
Suhas N
Devika H
Shekar Patil
Satheesh Chiradoni Thungappa
Somorat Bhattacharjee
Sridhar P.S
Roshni Dasgupta
Mohammed Naseer
Srinivas B.J
Vishal Rao
Veena Ramaswamy
Radheshyam Naik
Govind Babu
Aarthi Ravichandran
Urvashi Bahadur
Krithika Murugan
Mahesh B
Lohith Reddy
Ajaikumar Basavalinga S
Comprehensive genomic profiling reveals a unique genomic landscape in solid tumors in an Indian cancer cohort of 1000 patients: a single institutional experience
Scientific Reports
Comprehensive genomic profiling
Next-generation sequencing
Precision oncology
Targeted therapy
Immunotherapy
Multidisciplinary molecular tumor board
title Comprehensive genomic profiling reveals a unique genomic landscape in solid tumors in an Indian cancer cohort of 1000 patients: a single institutional experience
title_full Comprehensive genomic profiling reveals a unique genomic landscape in solid tumors in an Indian cancer cohort of 1000 patients: a single institutional experience
title_fullStr Comprehensive genomic profiling reveals a unique genomic landscape in solid tumors in an Indian cancer cohort of 1000 patients: a single institutional experience
title_full_unstemmed Comprehensive genomic profiling reveals a unique genomic landscape in solid tumors in an Indian cancer cohort of 1000 patients: a single institutional experience
title_short Comprehensive genomic profiling reveals a unique genomic landscape in solid tumors in an Indian cancer cohort of 1000 patients: a single institutional experience
title_sort comprehensive genomic profiling reveals a unique genomic landscape in solid tumors in an indian cancer cohort of 1000 patients a single institutional experience
topic Comprehensive genomic profiling
Next-generation sequencing
Precision oncology
Targeted therapy
Immunotherapy
Multidisciplinary molecular tumor board
url https://doi.org/10.1038/s41598-025-94762-z
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