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Attend this session at the
2018 ASCO Annual Meeting!


Session: Tumor Testing in Precision Oncology: From Heredity to Counseling to Implementation

Type: Clinical Science Symposium

Time: Monday June 4, 8:00 AM to 9:30 AM

Location: S102

Pan-cancer microsatellite instability to predict for presence of Lynch syndrome.

Sub-category:
Genetic Testing

Category:
Cancer Prevention, Hereditary Genetics, and Epidemiology

Meeting:
2018 ASCO Annual Meeting

Abstract No:
LBA1509

Citation:
J Clin Oncol 36, 2018 (suppl; abstr LBA1509)

Author(s): Alicia Latham Schwark, Preethi Srinivasan, Yelena Kemel, Jinru Shia, Chaitanya Bandlamudi, Diana Mandelker, Marianne Dubard-Gault, Christina Tran, Sumit Middha, Jaclyn Frances Hechtman, Alexander Penson, Anna M. Varghese, Liying Zhang, Mark E. Robson, David B. Solit, Luis A. Diaz, Barry S. Taylor, Kenneth Offit, Michael F. Berger, Zsofia Kinga Stadler; Memorial Sloan Kettering Cancer Center, New York, NY

Abstract Disclosures

Abstract:

Background: The success of immunotherapy in microsatellite unstable (MSI-H) and/or DNA mismatch repair deficient (MMR-D) tumors has resulted in routine MSI-H/MMR-D testing in advanced solid tumors. Unlike colorectal (CRC) and endometrial cancer (EC), where this has long been undertaken, the characterization of Lynch syndrome (LS) across heterogeneous MSI-H/MMR-D tumors is unknown. Methods: Through a targeted NGS panel, MSI status was determined via MSIsensor. Scores of < 3, ≥3 to < 10, or ≥10 designated Microsatellite stable (MSS), MSI-Indeterminate (MSI-I) or MSI-H status, respectively. Germline mutations were assessed in MLH1, MSH2, MSH6, PMS2, EPCAM. Immunohistochemical staining (IHC) for MMR-D and tumor signatures in LS patients were assessed. Clinical variables were correlated with MSI and compared via Chi square or T-test. Results: Of 15,045 tumors spanning > 50 cancers , 93.2% were MSS, 4.6% MSI-I, and 2.2% MSI-H. Germline mutations were identified in 0.3% (37/14,020), 1.9% (13/699), and 16.3% (53/326) in the MSS, MSI-I, and MSI-H groups, respectively (p-value < 0.001). 25% of 1,025 MSI-H/MSI-I tumors were CRC/EC, but 50% (33/66) of LS patients had MSI-H/MSI-I tumors less commonly or not previously associated with LS (mesothelioma, sarcoma, adrenocortical, melanoma, ovarian germ cell). LS pts with MSI-H/MSI-I non-CRC/EC tumors only met testing criteria in 63.6% of cases, had lower MSIsensor scores, and were more likely to be MSI-I (MSI-I: non-CRC/EC, 30.3% (10/33) vs CRC/EC 9.1% (3/33); p-value = 0.03). IHC was completed in 86.4% (57/66) of LS MSI-H/MSI-I tumors, with 98.3% MMR-D-concordance. Of LS pts with MSS tumors, 78% had MSH6/PMS2 mutations, but 71% of LS pts with MSI-H/MSI-I tumors had MLH1/MSH2/EPCAM mutations(p-value < 0.001). 89% (33/37) of MSS tumors of LS pts had non-MMR-D signatures. Conclusions: MSI-H/MMR-D is predictive of LS across tumor types and suggests a more heterogeneous spectrum of LS-associated cancers than previously appreciated. Nearly 40% of LS pts with MSI-H/MMR-D non-CRC/EC tumors did not meet clinical criteria for genetic testing, suggesting that MSI-H/MMR-D tumors, regardless of cancer type or family history, should prompt germline testing for the evaluation of LS.

 
Other Abstracts in this Sub-Category:

 

1. Frequency of actionable cancer predisposing germline mutations in patients with lung cancers.

Meeting: 2018 ASCO Annual Meeting Abstract No: 1504 First Author: Semanti Mukherjee
Category: Cancer Prevention, Hereditary Genetics, and Epidemiology - Genetic Testing

 

2. Validation of a combined residual risk score for healthy unaffected women presenting to breast cancer (BC) screening centers.

Meeting: 2018 ASCO Annual Meeting Abstract No: 1507 First Author: Kathryn Dalton
Category: Cancer Prevention, Hereditary Genetics, and Epidemiology - Genetic Testing

 

3. Disclosure of secondary germline findings from clinical tumor-normal paired somatic mutation profiling.

Meeting: 2018 ASCO Annual Meeting Abstract No: 1510 First Author: Molly S. Daniels
Category: Cancer Prevention, Hereditary Genetics, and Epidemiology - Genetic Testing

 

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