Some driver RET mutations are not observed in Indian cancers

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The impact of two driver mutations of RET gene, V804M/L and S891A, on Thyroid cancer was described recently by Pichardo et al in JAMA Otolaryngology, 2023. In a population screening, 75 people were identified to have 2 Pathogenic or Likely Pathogenic (P/LP) germline variants of the RET gene. 20 out of these 75 patients chose to undergo prophylactic thyroidectomy even though they did not have any symptoms of cancer. After surgery, pathological analysis of their tissue detected the growth of medullary or papillary thyroid cancer (PTC) in 12 and 2 patients respectively, i.e., 70% of patients with these 2 mutations had been harboring cancer unknowingly!
We examined the presence of these 2 RET variants in Sapien’s 61 Indian thyroid cancer samples profiled in the OncoMineDx panel by ThermoFisher. P/LP mutations were seen in 4 cases, all below the age of 40. Three cases were PTCs and 1 Follicular, with an overall percentage of 6%. The variants detected were V804M/L (3 cases) and C618Y (1 case, Follicular). No case of S891A mutation was detected.
We also checked for RET mutations in our genetically profiled lung cancers (103 cases) where 28 cases had SNVs with 5 cases of V804M, and 1 case had a fusion. No case of S891A was observed. Similarly, among 449 breast cancers, 280 CRCs, 47 gliomas and few cases each of endometrium, urinary bladder and prostate cancers that have been genetically profiled, many cases of V804M/L and other P/LP RET mutations were observed but none of S891A.

Genetic Counselling an Personalized Medicine conference in Hyderabad

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Delighted to be a part of 8th Annual BGCI #conference held at the #University of Hyderabad from July 7th to 9th, 2023 where Rakesh Sharma, PhD and Madhuri R presented posters titled “Molecular landscape of #lung adenocarcinoma in India for personalizing therapy” and “Driver gene alterations in EGFR and IDH1 are mutually exclusive in Indian Gliomas”.

Jugnu Jain and Kalpana Kannabiran were invited by Dr Q. Annie Hasan to chair the session on “Psychosocial #ethical and legal issues in #genetics and #genomics ” including panelists Dhavendra kumar Mahati Chittem Saveetha Meganathan, Kelly Ormond and Peter Abad.
Reena Trivedi Vaishnavi Suresh helped put the panel together.

It was an enriching experience, filled with insightful presentations and discussions.

Mismatch repair deficiency tested in seven cancer types

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Sapien is surveying different #tumor types in its #biobank for mismatch repair-deficiency (MMR-D), also called microsatellite instability (MSi-High). This is because #colorectalcancer #patients with MMR-D do not respond well to standard #chemotherapy but do respond to immune checkpoint inhibitors or ICI. To see which other #cancers may benefit from immune checkpoint inhibitors such as #PD1, we tested 500 curated cases of Endometrial, H&N, Kidney, Liver, Gastric and Thyroid cancers and compared them to 165 colorectal cancers by IHC.
We observe that H&N, Liver and Thyroid cancer have low MMR-D. However, Endometrial cancers have 4-5 times higher MMR-D as compared to CRC; Stomach and Renal cancers also have 5-6% MMR-D cases. Our data suggests that immune checkpoint inhibitors may greatly improve the response rate and survival of Endometrial, Stomach and Kidney cancers in addition to CRC.

HER2 Oncogenic mutations and amplifications are common across many Indian solid tumors

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Until recently, HER2 (or ErbB2) targeting drugs were only approved for HER2-amplified breast & gastric cancers. FDA has now granted accelerated approval for trastuzumab or Enhertu to treat lung cancer patients bearing activating HER2 mutations. We analyzed our data of ~1000 solid cancer cases generated using the OncomineTM Dx NGS panel to determine the pattern of ERBB2 amplification vs. mutations. We see that in some cancers, amplifications are more common (breast, gastric, endometrial cancers) but in others, activating mutations are more common (colorectal, lung, thyroid and gliomas) with the most common mutation being V842I in Indian samples. Molecular insights gained from such NGS analysis can hopefully improve precision medicine by expanding the use of approved HER2-targeting drugs for colorectal, endometrial, gliomas, thyroid and other cancer patients that are likely to benefit from them.

Digital library of whole slide Images Built at Sapien

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Sapien is focusing on the emerging area of Digital Pathology combined with Machine Learning (ML) and Artificial Intelligence (AI), to improve the diagnoses, to sub-classify patients into more clinically-relevant phenotypes and predict outcomes. Sophisticated image analysis tools combined with computational advances allow whole slide images (WSI) to be analysed using ML / AI to develop algorithms to aid pathologists and clinicians to personalize treatment.
 
For this purpose, Sapien is creating a high-resolution library of WSI from hundreds of cancer specimens’ FFPE blocks for which demographic and diagnostic data has already been curated and structured by the biobank.
In breast cancer for example, matched sets of H&E, ER, PR, HER2, Ki67/MIB images from the same case have been scanned at 40X magnification from 750+ cases, spanning all stages, grades and histotypes in pathology. Even benign breast tumors as well as normal breast tissues have been scanned as controls. Multiple scanners (Philips, Morphle, Motic) are being used to also allow normalization across different platforms for solutions.
 
ImageNet, IBM, TCGA have large image datasets in oncology; Sapien’s digital library is the largest such database for Indian cancer patients. Sapien is adding treatment and outcomes data, as well as genetic variant data, to these cancer cases, in the hope of deep learning approaches making it possible for the inexpensive, more widely available HE images to replace the need for IHC-, FISH- and gene-based biomarker analysis.
https://www.ibm.com/blogs/research/2020/03/benefits-ai-for-breast-cancer-detection/
https://www.sciencedirect.com/science/article/pii/S2153353922003510
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037318/

Dr. Jugnu Jain, CEO, delivering an invited talk on “Sustainability of Biobanking in India” at the workshop on Biobanking organized by ILBS, New Delhi.

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Quatramer’s tunability stems from the fact that the system can be modified and adjusted to deliver single or multiple ratios of payloads in order to optimize synergistic mechanisms of action in lower doses.

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Our paper is out in Frontiers in Pharmacology

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Our paper on first ever reported establishment of a cell culture from a rare brain tumor (DIG glioma), is published in Frontiers in Pharmacology journal, with Impact factor of 4.5. Such primary cultures are very useful for drugdevelopment and phenotypic screening.

https://www.frontiersin.org/articles/10.3389/fphar.2022.778193/full?&utm_source=Email_to_authors_&utm_medium=Email&utm_content=T1_11.5e1_author&utm_campaign=Email_publication&field=&journalName=Frontiers_in_Pharmacology&id=778193

Sapien’s work for Hillstream BioPharma presented at AACR

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Sapien biobank evaluates novel drug candidates and formulations for global biotech and pharma companies using our proprietary panel of live cells and 3Dcellculture derived from cancer surgeries tissues. These are also called patient-derived cells or PDCs. Assays using PDCs are very valuable before going to clinical trials. We are delighted that our work done with a novel formulation in triple negative breastcancer (TNBC) proliferation and stemcell viability was included for the presentation at AACR.