{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T22:59:14Z","timestamp":1783292354388,"version":"3.54.6"},"reference-count":33,"publisher":"Scientific Scholar","content-domain":{"domain":["ijmr.org.in"],"crossmark-restriction":true},"short-container-title":["Indian J Med Res"],"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Genomic studies are essential for identifying mutations that may influence key aspects of breast tumours, such as susceptibility, aggressiveness, and response to treatment. There are deficient molecular and genomic data from Indian breast cancer patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>mRNA from primary breast cancer samples were subjected to next-generation transcriptome (mRNA) sequencing on an Illumina platform, in duplicates and triplicates to generate 30\u201360 M reads\/sample. PAM50, and absolute intrinsic molecular subtyping (AIMS) gene expression-based classifiers were used for intrinsic subtyping. Variants were called using, GATK, MuTect2, VarScan2, and VarDict, followed by filtering for somatic and non-synonymous changes. Germline variants were excluded using public databases. ClinVar annotations prioritised pathogenic variants, and the STRING algorithm was used for network analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 207 RNA-Seq datasets from 97 breast cancer patients were analysed. There was good concordance between the immunohistochemical receptor and AIMS classification for all subtypes, but there was discordance between immunohistochemical and PAM50 subtypes within the ER-positive\/HER2-positive subgroup, wherein only 38.5% (n= 5) were classified as HER2-like by gene expression classification. Variant analysis identified 145 high-confidence somatic mutations, with\n                      <jats:italic>TP53<\/jats:italic>\n                      (n=46, 47%) and\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      (n=33, 34%) being the most frequent. Additional actionable mutations in\n                      <jats:italic>BRCA1<\/jats:italic>\n                      ,\n                      <jats:italic>BRCA2<\/jats:italic>\n                      ,\n                      <jats:italic>FGFR2<\/jats:italic>\n                      ,\n                      <jats:italic>PTEN<\/jats:italic>\n                      ,\n                      <jats:italic>AKT1,<\/jats:italic>\n                      and\n                      <jats:italic>mTOR<\/jats:italic>\n                      pathways were identified. At least one actionable mutation was found in 52% of patients. Fusion transcript analysis identified 91 recurrent fusions, including novel partners with\n                      <jats:italic>ERBB2<\/jats:italic>\n                      ,\n                      <jats:italic>MED1<\/jats:italic>\n                      , and\n                      <jats:italic>CDK12<\/jats:italic>\n                      , suggesting the possibility of unique molecular events.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation and conclusions<\/jats:title>\n                    <jats:p>This study demonstrates that Indian breast cancer patients exhibit molecular subtypes and actionable mutations comparable to Caucasian cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.25259\/ijmr_1642_2024","type":"journal-article","created":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T16:26:10Z","timestamp":1772382370000},"page":"95-103","update-policy":"https:\/\/doi.org\/10.25259\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinically actionable alterations in Indian breast cancer patients derived through whole transcriptome sequencing"],"prefix":"10.25259","volume":"163","author":[{"given":"Nilesh","family":"Gardi","sequence":"first","affiliation":[{"name":"Clinician Scientist Laboratory, Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Centre, Mumbai, Maharashtra, India"},{"name":"Training School Complex, Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Clinician Scientist Laboratory, Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Centre, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan","family":"Chaubal","sequence":"additional","affiliation":[{"name":"Clinician Scientist Laboratory, Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Centre, Mumbai, Maharashtra, India"},{"name":"Training School Complex, Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Surgical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khushboo A.","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Clinician Scientist Laboratory, Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Centre, Mumbai, Maharashtra, India"},{"name":"Training School Complex, Homi Bhabha National Institute, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anushree","family":"Kadam","sequence":"additional","affiliation":[{"name":"Clinician Scientist Laboratory, Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Centre, Mumbai, Maharashtra, India"},{"name":"Training School Complex, Homi Bhabha National Institute, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankita","family":"Singh","sequence":"additional","affiliation":[{"name":"Clinician Scientist Laboratory, Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Centre, Mumbai, Maharashtra, India"},{"name":"Training School Complex, Homi Bhabha National Institute, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishwarya Sabari","family":"Raja","sequence":"additional","affiliation":[{"name":"Clinician Scientist Laboratory, Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Centre, Mumbai, Maharashtra, India"},{"name":"Training School Complex, Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaibhav","family":"Vanmali","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohini","family":"Hawaldar","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhani","family":"Sale","sequence":"additional","affiliation":[{"name":"Clinician Scientist Laboratory, Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Centre, Mumbai, Maharashtra, India"},{"name":"Training School Complex, Homi Bhabha National Institute, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalaka","family":"Joshi","sequence":"additional","affiliation":[{"name":"Training School Complex, Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Surgical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra","family":"Badwe","sequence":"additional","affiliation":[{"name":"Training School Complex, Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Surgical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeep","family":"Gupta","sequence":"additional","affiliation":[{"name":"Clinician Scientist Laboratory, Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Centre, Mumbai, Maharashtra, India"},{"name":"Training School Complex, Homi Bhabha National Institute, Mumbai, Maharashtra, India"},{"name":"Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10894","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"10.25259\/IJMR_1642_2024\/ref-1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4137\/BIC.S3793","article-title":"Identification of gene expression signature in estrogen receptor positive breast carcinoma","volume":"2","author":"Thakkar","year":"2010","journal-title":"Biomark Cancer."},{"key":"10.25259\/IJMR_1642_2024\/ref-2","doi-asserted-by":"publisher","first-page":"10018","DOI":"10.1038\/s41598-019-46261-1","article-title":"Study of gene expression profiles of breast cancers in Indian women","volume":"9","author":"Malvia","year":"2019","journal-title":"Sci Rep."},{"key":"10.25259\/IJMR_1642_2024\/ref-4","doi-asserted-by":"publisher","first-page":"932060","DOI":"10.3389\/fgene.2022.932060","article-title":"Transcriptomic profiling of Indian breast cancer patients revealed subtype\u2013specific mRNA and lncRNA signatures","volume":"13","author":"Manjunath","year":"2022","journal-title":"Front Genet."},{"key":"10.25259\/IJMR_1642_2024\/ref-5","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1158\/2767-9764.CRC-23-0277","article-title":"natural history of germlineBRCA1 mutated and BRCA wild\u2013type triple\u2013negative breast cancer","volume":"4","author":"Gardi","year":"2024","journal-title":"Cancer Res Commun."},{"key":"10.25259\/IJMR_1642_2024\/ref-6","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/s42003-025-07606-x","article-title":"Genomic hallmarks of endocrine therapy resistance in ER\/PR+HER2\u2013 breast tumours","volume":"8","author":"Ghosh","year":"2025","journal-title":"Commun Biol."},{"key":"10.25259\/IJMR_1642_2024\/ref-7","doi-asserted-by":"publisher","first-page":"391","DOI":"10.4103\/0019-509X.92245","article-title":"Estrogen, progesterone and HER2 receptor expression in breast tumors of patients, and their usage of HER2\u2013targeted therapy, in a tertiary care centre in India","volume":"48","author":"Ghosh","year":"2011","journal-title":"Indian J Cancer."},{"key":"10.25259\/IJMR_1642_2024\/ref-8","doi-asserted-by":"publisher","first-page":"16","DOI":"10.4103\/ijc.IJC_484_17","article-title":"Breast cancer in a tertiary cancer center in India \u2013 An audit, with outcome analysis","volume":"55","author":"Nair","year":"2018","journal-title":"Indian J Cancer."},{"key":"10.25259\/IJMR_1642_2024\/ref-9","doi-asserted-by":"publisher","first-page":"e2200126","DOI":"10.1200\/GO.22.00126","article-title":"Clinical profile and outcome of patients with human epidermal growth factor receptor 2\u2013positive breast cancer with brain metastases: Real\u2013world experience","volume":"8","author":"Bhargava","year":"2022","journal-title":"JCO Glob Oncol."},{"key":"10.25259\/IJMR_1642_2024\/ref-10","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/s10549-018-4749-3","article-title":"Pre\u2013operative progesterone benefits operable breast cancer patients by modulating surgical stress","volume":"170","author":"Chatterjee","year":"2018","journal-title":"Breast Cancer Res Treat."},{"key":"10.25259\/IJMR_1642_2024\/ref-11","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1158\/1541-7786.MCR-23-0265","article-title":"Surgical tumor resection deregulates hallmarks of cancer in resected tissue and the surrounding microenvironment","volume":"22","author":"Chaubal","year":"2024","journal-title":"Mol Cancer Res."},{"key":"10.25259\/IJMR_1642_2024\/ref-12","doi-asserted-by":"publisher","first-page":"2690","DOI":"10.1016\/j.celrep.2019.04.098","article-title":"The genomic and immune landscapes of lethal metastatic breast cancer","volume":"27","author":"De Mattos\u2013Arruda","year":"2019","journal-title":"Cell Rep."},{"key":"10.25259\/IJMR_1642_2024\/ref-13","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1093\/jnci\/dju357","article-title":"Absolute assignment of breast cancer intrinsic molecular subtype","volume":"107","author":"Paquet","year":"2014","journal-title":"J Natl Cancer Inst."},{"key":"10.25259\/IJMR_1642_2024\/ref-14","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias\u2013aware quantification of transcript expression","volume":"14","author":"Patro","year":"2017","journal-title":"Nat Methods."},{"key":"10.25259\/IJMR_1642_2024\/ref-15","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.12688\/f1000research.7563.2","article-title":"Differential analyses for RNA\u2013seq: Transcript\u2013level estimates improve gene\u2013level inferences","volume":"4","author":"Soneson","year":"2015","journal-title":"F1000Res."},{"key":"10.25259\/IJMR_1642_2024\/ref-16","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA\u2013seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics."},{"key":"10.25259\/IJMR_1642_2024\/ref-17","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The genome analysis toolkit: A map reduce framework for analyzing next\u2013generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"10.25259\/IJMR_1642_2024\/ref-18","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nbt.2514","article-title":"Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples","volume":"31","author":"Cibulskis","year":"2013","journal-title":"Nat Biotechnol."},{"key":"10.25259\/IJMR_1642_2024\/ref-19","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1101\/gr.129684.111","article-title":"VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencing","volume":"22","author":"Koboldt","year":"2012","journal-title":"Genome Res."},{"key":"10.25259\/IJMR_1642_2024\/ref-20","doi-asserted-by":"publisher","first-page":"e108","DOI":"10.1093\/nar\/gkw227","article-title":"VarDict: A novel and versatile variant caller for next\u2013generation sequencing in cancer research","volume":"44","author":"Lai","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.25259\/IJMR_1642_2024\/ref-21","doi-asserted-by":"publisher","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: Functional annotation of genetic variants from high\u2013throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"10.25259\/IJMR_1642_2024\/ref-22","doi-asserted-by":"publisher","first-page":"D925","DOI":"10.1093\/nar\/gkae977","article-title":"The evolution of dbSNP: 25 years of impact in genomic research","volume":"53","author":"Phan","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"10.25259\/IJMR_1642_2024\/ref-23","doi-asserted-by":"publisher","first-page":"D1210","DOI":"10.1093\/nar\/gkad986","article-title":"COSMIC: A curated database of somatic variants and clinical data for cancer","volume":"52","author":"Sondka","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"10.25259\/IJMR_1642_2024\/ref-24","doi-asserted-by":"publisher","first-page":"baac029","DOI":"10.1093\/database\/baac029","article-title":"TMC\u2013SNPdb 2.0: An ethnic\u2013specific database of Indian germline variants","volume":"2022","author":"Desai","year":"2022","journal-title":"Database (Oxford)."},{"key":"10.25259\/IJMR_1642_2024\/ref-25","doi-asserted-by":"publisher","first-page":"D1225","DOI":"10.1093\/nar\/gkaa923","article-title":"IndiGenomes: A comprehensive resource of genetic variants from over 1000 Indian genomes","volume":"49","author":"Jain","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"10.25259\/IJMR_1642_2024\/ref-26","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1093\/nar\/29.1.308","article-title":"dbSNP: The NCBI database of genetic variation","volume":"29","author":"Sherry","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"10.25259\/IJMR_1642_2024\/ref-27","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1093\/nar\/28.1.352","article-title":"dbSNP: A database of single nucleotide polymorphisms","volume":"28","author":"Smigielski","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"10.25259\/IJMR_1642_2024\/ref-28","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1038\/s41587-019-0055-9","article-title":"The International cancer genome consortium data portal","volume":"37","author":"Zhang","year":"2019","journal-title":"Nat Biotechnol."},{"key":"10.25259\/IJMR_1642_2024\/ref-29","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"10.25259\/IJMR_1642_2024\/ref-30","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/s13059-019-1842-9","article-title":"Accuracy assessment of fusion transcript detection via read\u2013mapping and de novo fusion transcript assembly\u2013based methods","volume":"20","author":"Haas","year":"2019","journal-title":"Genome Biol."},{"key":"10.25259\/IJMR_1642_2024\/ref-31","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41698-024-00555-4","article-title":"Recurrent UBE3C\u2013LRP5 translocations in head and neck cancer with therapeutic implications","volume":"8","author":"Dharavath","year":"2024","journal-title":"NPJ Precis Oncol."},{"key":"10.25259\/IJMR_1642_2024\/ref-32","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1093\/annonc\/mdy263","article-title":"A framework to rank genomic alterations as targets for cancer precision medicine: The ESMO scale for clinical actionability of molecular targets (ESCAT)","volume":"29","author":"Mateo","year":"2018","journal-title":"Ann Oncol."},{"key":"10.25259\/IJMR_1642_2024\/ref-33","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13073-018-0531-8","article-title":"Cancer Genome Interpreter annotates the biological and clinical relevance of tumor alterations","volume":"10","author":"Tamborero","year":"2018","journal-title":"Genome Med."},{"key":"10.25259\/IJMR_1642_2024\/ref-34","doi-asserted-by":"publisher","first-page":"85","DOI":"10.4103\/ijmr.ijmr_1574_22","article-title":"Methylation of BRCA1 promoter in sporadic breast cancer","volume":"158","author":"Jagtap","year":"2023","journal-title":"Indian J Med Res."}],"container-title":["The Indian Journal of Medical Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ijmr.org.in\/clinically-actionable-alterations-in-indian-breast-cancer-patients-derived-through-whole-transcriptome-sequencing\/","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/ijmr.org.in\/clinically-actionable-alterations-in-indian-breast-cancer-patients-derived-through-whole-transcriptome-sequencing\/","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T08:17:04Z","timestamp":1773303424000},"score":1,"resource":{"primary":{"URL":"http:\/\/ijmr.org.in\/clinically-actionable-alterations-in-indian-breast-cancer-patients-derived-through-whole-transcriptome-sequencing\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,28]]},"references-count":33,"alternative-id":["10.25259\/IJMR_1642_2024"],"URL":"https:\/\/doi.org\/10.25259\/ijmr_1642_2024","relation":{},"ISSN":["0971-5916"],"issn-type":[{"value":"0971-5916","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2,28]]},"article-number":"95"}}