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Brief Profile of the Awardee

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Dr Amit Dutt

  • 2017
  • Medical Sciences
  • 06/09/1973
  • Cancer Genomics: interpretation, characterization, and translation of genomic discoveries to clinics
Award Citation:

Dr Dutt has made outstanding contributions to cancer genetics especially related to the FGF Receptor family in lung cancer, including novel mutations in Indian patients. This has major implications for our understanding of the disease as well as translational possibilities.

Academic Qualifications:
SNODegreeSubjectCGP/MarksYearUniversityAdditional Particular
1M.Sc.Biosciences711997Jamia Millia Islamia 
2P.G. DiplomaBiochemical Technology711996Delhi UniversitySri Venkateswara College
       
Thesis and Guide details:
SNOTitle of Ph.D. ThesisName of Guide
1Characterization of the Rhomboid Homolog ROM-1 as a Positive Regulator of the RAS/MAPK Pathway in Caenorhabditis elegansProf. Dr. Alex Hajnal (University of Zurich, Switzerland)
   
Details of CSIR Fellowship/ Associateship held, if any or from other sources/ agencies.
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Significant foreign assignments:
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(a) Significant contributions to science and/ or technology development by the nominee based on the work done in India during most part of last 5 years:
In India, Dr. Dutt began with addressing a germane and basic deficiency in the field of cancer research. His pioneering work (involving a large cohort of 1000 odd samples) establishes that while EGFR mutations are present in over 30% of East Asian and 10% of Caucasian lung adenocarcinoma patients, they are only found in about 23-25% of Indian lung adenocarcinoma patients (PLoS One 2013 Apr; PLoS One 2013 Oct; Ind J Cancer 2013; F1000Res 2015). Similarly, KRAS mutations are present at 60% lower frequency in Indian lung adenocarcinoma patients than compared to the Caucasian population (Br J Cancer 2014). This work has received a cumulative citation of over 85 times in last few years that underlies the significance of his contribution made to the field. In his continued effort, Dr. Dutt’s more recent work establishes landscape of actionable mutations beyond EGFR and KRAS in Indian lung cancer patients (Annals of Oncology 2016). Taken together, these study forms a crucial basis to rationalize targeted therapy in India and to adopt genetic testing in a clinical diagnostic laboratory at an affordable pricing—as the genetic test developed by Dr. Dutt and colleagues to genotype EGFR mutations has been able to remarkably reduce its cost from ~$200 to $12 per test (!) that is now being offered at the Tata Memorial Hospital on routine basis—enabling and transforming the way EGFR mutation profiling is been carried out at an affordable cost for every lung cancer patient. Dr. Dutt’s another seminal contribution from ACTREC includes an in-depth functional characterization of FGFR1 and FGFR3 alterations as novel candidate therapeutic targets in lung cancer (PLoS One 2011; Annals of Oncology 2016), which has received over 286 citations in literature. Dr. Dutt’s work using elegant genetic, biochemical and mousexenograft based mechanistic characterization led to the discovery of FGFR3 activating mutations in lung adenocarcinoma patients of Indian origin. Amit’s work thus opens a possibility for cancer treatment. Beyond lung cancer, Dr. Dutt’s work demonstrates that a considerable fraction of non-smoker tongue cancer patients of Indian origin with nodal positivity are driven by upregualtion of Notch pathway. This result underscores NOTCH1 as a therapeutic target in these tongue cancer patients (BMC Genomics 2015; Oncotarget 2016). Similarly, Dr. Dutt described the first report of MYOD1 (L122R) mutation in a large cohort of 49 rhabdomyosarcoma (RMS) reported so far, as a single study, to identify an aggressive subset of spindle cell/sclerosing RMS patients to help inform adoption of appropriate therapeutic regimen (Modern Pathology 2016). Dr. Dutt and group has also presented the first evidence to support the association of non-typhoidal Salmonella species along with typhoidal isolates in gallbladder cancer of Indian origin, which has its implication in disease management (Br J Cancer 2015; Infectious Agents and Cancer 2015). In a different aspect, other major significant contributions made by Dr. Dutt from his laboratory at ACTREC include a classic and humongous effort taken by him to fill in the gap in the field due to lack of Indian specific germline normal SNP database.
(b) Impact of the contributions in the field concerned:
Dr. Dutt’s contribution has been phenomenal to the field. I anticipate Dr. Dutt’s continued contribution to the field to have a major impact in the field of cancer research that would eventually lead to cancer treatment! Specifically, the discovery of activating FGFR1 amplification in lung squamous and FGFR3 mutations in lung adenocarcinoma subtypes, underscores that FGFR family may potentially join the EGFR family as a widespread target for therapeutic intervention in human lung cancers. Similarly, Dr. Dutt’s comprehensive description of the landscape of actionable mutations in Indian lung cancer patients forms the basis to rationalize targeted therapy in India in an informed manner, and adopt genetic testing in a clinical diagnostic laboratory at an affordable pricing. In addition to his work on lung cancer, following major contribution were made in the last 5 yrs with significant impact in the field: 1. Dr. Dutt and his groupd has presented the first evidence describing association of Notch pathway activation with nodal positivity and non-smoking status in early tongue cancer patients of Indian origin. Dr. Dutt showed that inhibition of NOTCH activation by gamma secretase inhibitor or shRNA mediated knockdown of NOTCH1 inhibits spheroid forming capacity, transformation, survival and migration of the HNSCC cells suggesting an oncogenic role of NOTCH1 in TSCC. These results could be the basis for therapeutic targeting of NOTCH1 in tongue cancer (Oncotarget 2016) IF 6.4. 2. Dr. Dutt presented the first report of MYOD1 (L122R) mutation in a large cohort of 49 rhabdomyosarcoma (RMS) reported so far, as a single study that is associated with a relatively aggressive clinical course. Based on these findings, MYOD1 (L122R) mutation genotyping may preclude the requirement to perform IHC analysis to identify an aggressive subset of spindle cell/sclerosing RMS patients early on to help inform adoption of appropriate therapeutic regimen (Modern Pathology 2016) IF 6.1. 3. In a classic and humongous effort to fill the void due to lack of Indian germline variant database, Dr. Dutt developed the TMC-SNPdb— first Indian SNP reference database. The TMC-SNPdb is an open source freely available, flexible and upgradable database derived from whole exome data of 62 normal samples that will find its application for researchers studying various human diseases (Database 2016), including cancer research. It comes with a companion tool for biologist (with no computational background) to deplete Indian specific SNPs from their datasets using an intuitive graphic user interface. The TMC-SNPdb has been accepted as an integral part of dbSNP build145 and included in the Annovar package for world-wide accessibility. (Database 2016) IF 3.9. 4. Dr. Dutt and his group has presented the first evidence to support the association of non-typhoidal Salmonella species along with typhoidal isolates in gallbladder cancer, which may play a role in analogous to Helicobacter pylori in gastric cancer and Fusobacterium in colon cancer, with implication in disease management and therapeutic approach. The focus of treatment in typhoid-endemic countries such as India has historically been solely on eliminating typhoidal Salmonella species often underestimating the contribution of the non-typhoidal isolates that show an inherent higher resistance to the standard antibiotics resulting in their ability to lead to chronic carrier state in humans.
Places where work of last 5 years has been referred/ cited in Books, Reviews:
(i). Paper Cited
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(ii). Book Cited
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Names of the industries in which the technology (ies) has (have) been used :
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The achievements already been recognised by Awards by any learned body:
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The Awardee a fellow of the Indian National Science Academy/Indian Academy of Sciences/National Academy of Sciences/Others:
The Awardee delivered invited lecture(s) in India/abroad and/or chaired any scientific Internatiional Conference Symposium:
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List of Awardee's 10 most significant publications.
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List of Awardee's 5 most significant publications during the last 5 years
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List of Awardee's 5 most significant publications from out of work done in India during the last five years:
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Complete list of publications in standard refereed journals:
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Complete list of publications with foreign collaborators (indicating your status as author):
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List of papers published in Conferences /Symposia/ Seminars, etc:
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List of the most outstanding Technical Reports/ Review Articles:
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Statement regarding collaboration with scientists abroad:
List of Patents taken
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Total number of patents granted in last five years.
Details of Books published:
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Contact Details


  • Advanced Centre for Treatment, Research and Education in Cancer
    Tata Memorial Centre
    Sector 22 Kharghar
    Navi Mumbai - 410210
    Maharashtra INDIA
  • 022 2740 5000
  • 022 2740 5085
  • adutt[at]actrec[dot]gov[dot]in
19 Nov 2017, http://ssbprize.gov.in/Content/Detail.aspx?AID=532