Person:
Huang, Franklin

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Huang

First Name

Franklin

Name

Huang, Franklin
Author's Publications: search.filters.isAuthorOfPublication.0b7b6a88-87ae-460b-88c4-11c0a7357886

Search Results

Now showing 1 - 5 of 5
  • Thumbnail Image
    Publication
    Launching an Interactive Cancer Projects Map: A Collaborative Approach to Global Cancer Research and Program Development
    (American Society of Clinical Oncology, 2015) Trimble, Edward L.; Chisti, Ali A.; Craycroft, Jane A.; Duncan, Kalina; Gupta, Manaswi; Gutierrez, Daniel; Rosenberg, Ilyana; Sharara, Nour; Sivaram, Sudha; Topazian, Hillary M.; Wang, Jing Jing; Williams, Makeda J.; Huang, Franklin; Bhatt, Ami S.
  • Thumbnail Image
    Publication
    Identification of novel prostate cancer drivers using RegNetDriver: a framework for integration of genetic and epigenetic alterations with tissue-specific regulatory network
    (BioMed Central, 2017) Dhingra, Priyanka; Martinez-Fundichely, Alexander; Berger, Adeline; Huang, Franklin; Forbes, Andre Neil; Liu, Eric Minwei; Liu, Deli; Sboner, Andrea; Tamayo, Pablo; Rickman, David S.; Rubin, Mark A.; Khurana, Ekta
    We report a novel computational method, RegNetDriver, to identify tumorigenic drivers using the combined effects of coding and non-coding single nucleotide variants, structural variants, and DNA methylation changes in the DNase I hypersensitivity based regulatory network. Integration of multi-omics data from 521 prostate tumor samples indicated a stronger regulatory impact of structural variants, as they affect more transcription factor hubs in the tissue-specific network. Moreover, crosstalk between transcription factor hub expression modulated by structural variants and methylation levels likely leads to the differential expression of target genes. We report known prostate tumor regulatory drivers and nominate novel transcription factors (ERF, CREB3L1, and POU2F2), which are supported by functional validation. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1266-3) contains supplementary material, which is available to authorized users.
  • Thumbnail Image
    Publication
    Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine
    (2013) Allen, Eliezer M. Van; Wagle, Nikhil; Stojanov, Petar; Perrin, Danielle L.; Cibulskis, Kristian; Marlow, Sara; Jane-Valbuena, Judit; Friedrich, Dennis C.; Kryukov, Gregory; Carter, Scott L.; McKenna, Aaron; Sivachenko, Andrey; Rosenberg, Mara; Kiezun, Adam; Voet, Douglas; Lawrence, Michael; Lichtenstein, Lee T.; Gentry, Jeff G.; Huang, Franklin; Fostel, Jennifer; Farlow, Deborah; Barbie, David; Gandhi, Leena; Lander, Eric; Gray, Stacy; Joffe, Steven; Janne, Pasi; Garber, Judy; MacConaill, Laura; Lindeman, Neal; Rollins, Barrett; Kantoff, Philip; Fisher, Sheila A.; Gabriel, Stacey; Getz, Gad; Garraway, Levi
    Translating whole exome sequencing (WES) for prospective clinical use may impact the care of cancer patients; however, multiple innovations are necessary for clinical implementation. These include: (1) rapid and robust WES from formalin-fixed paraffin embedded (FFPE) tumor tissue, (2) analytical output similar to data from frozen samples, and (3) clinical interpretation of WES data for prospective use. Here, we describe a prospective clinical WES platform for archival FFPE tumor samples. The platform employs computational methods for effective clinical analysis and interpretation of WES data. When applied retrospectively to 511 exomes, the interpretative framework revealed a “long tail” of somatic alterations in clinically important genes. Prospective application of this approach identified clinically relevant alterations in 15/16 patients. In one patient, previously undetected findings guided clinical trial enrollment leading to an objective clinical response. Overall, this methodology may inform the widespread implementation of precision cancer medicine.
  • Thumbnail Image
    Publication
    Rapid Intraoperative Molecular Characterization of Glioma
    (American Medical Association (AMA), 2015) Shankar, Ganesh; Francis, Joshua M.; Rinne, Mikael; Ramkissoon, Shakti H.; Huang, Franklin; Venteicher, Andrew S; Akama-Garren, Elliot H.; Kang, Yun Jee; Lelic, Nina; Kim, James C.; Brown, Loreal E.; Charbonneau, Sarah K; Golby, Alexandra; Sekhar Pedamallu, Chandra; Hoang, Mai; Sullivan, Ryan; Cherniack, Andrew D.; Garraway, Levi; Stemmer-Rachamimov, Anat; Reardon, David; Wen, Patrick; Brastianos, Priscilla; Curry, William; Barker, Frederick; Hahn, William; Nahed, Brian; Ligon, Keith; Louis, David; Cahill, Daniel; Meyerson, Matthew
    IMPORTANCE: Conclusive intraoperative pathologic confirmation of diffuse infiltrative glioma guides the decision to pursue definitive neurosurgical resection. Establishing the intraoperative diagnosis by histologic analysis can be difficult in low-cellularity infiltrative gliomas. Therefore, we developed a rapid and sensitive genotyping assay to detect somatic single-nucleotide variants in the telomerase reverse transcriptase (TERT) promoter and isocitrate dehydrogenase 1 (IDH1). OBSERVATIONS: This assay was applied to tissue samples from 190 patients with diffuse gliomas, including archived fixed and frozen specimens and tissue obtained intraoperatively. Results demonstrated 96% sensitivity (95% CI, 90%–99%) and 100% specificity (95% CI, 95%–100%) for World Health Organization grades II and III gliomas. In a series of live cases, glioma-defining mutations could be identified within 60 minutes, which could facilitate the diagnosis in an intraoperative timeframe. CONCLUSIONS AND RELEVANCE: The genotyping method described herein can establish the diagnosis of low-cellularity tumors like glioma and could be adapted to the point-of-care diagnosis of other lesions that are similarly defined by highly recurrent somatic mutations.
  • Thumbnail Image
    Publication
    Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden
    (BioMed Central, 2017) Chalmers, Zachary R.; Connelly, Caitlin F.; Fabrizio, David; Gay, Laurie; Ali, Siraj M.; Ennis, Riley; Schrock, Alexa; Campbell, Brittany; Shlien, Adam; Chmielecki, Juliann; Huang, Franklin; He, Yuting; Sun, James; Tabori, Uri; Kennedy, Mark; Lieber, Daniel S.; Roels, Steven; White, Jared; Otto, Geoffrey A.; Ross, Jeffrey S.; Garraway, Levi; Miller, Vincent A.; Stephens, Phillip J.; Frampton, Garrett M.
    Background: High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors and has been shown to be more significantly associated with response to PD-1 and PD-L1 blockade immunotherapy than PD-1 or PD-L1 expression, as measured by immunohistochemistry (IHC). The distribution of TMB and the subset of patients with high TMB has not been well characterized in the majority of cancer types. Methods: In this study, we compare TMB measured by a targeted comprehensive genomic profiling (CGP) assay to TMB measured by exome sequencing and simulate the expected variance in TMB when sequencing less than the whole exome. We then describe the distribution of TMB across a diverse cohort of 100,000 cancer cases and test for association between somatic alterations and TMB in over 100 tumor types. Results: We demonstrate that measurements of TMB from comprehensive genomic profiling are strongly reflective of measurements from whole exome sequencing and model that below 0.5 Mb the variance in measurement increases significantly. We find that a subset of patients exhibits high TMB across almost all types of cancer, including many rare tumor types, and characterize the relationship between high TMB and microsatellite instability status. We find that TMB increases significantly with age, showing a 2.4-fold difference between age 10 and age 90 years. Finally, we investigate the molecular basis of TMB and identify genes and mutations associated with TMB level. We identify a cluster of somatic mutations in the promoter of the gene PMS2, which occur in 10% of skin cancers and are highly associated with increased TMB. Conclusions: These results show that a CGP assay targeting ~1.1 Mb of coding genome can accurately assess TMB compared with sequencing the whole exome. Using this method, we find that many disease types have a substantial portion of patients with high TMB who might benefit from immunotherapy. Finally, we identify novel, recurrent promoter mutations in PMS2, which may be another example of regulatory mutations contributing to tumorigenesis. Electronic supplementary material The online version of this article (doi:10.1186/s13073-017-0424-2) contains supplementary material, which is available to authorized users.