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F1H Soft Tissue Sarcoma (NOS) Sample Report.Pdf PATIENT TUMOR TYPE REPORT DATE Soft tissue sarcoma (NOS) TRF# ABOUT THE TESTESTT FoundationOne®Heme is a comprehensive genomic profiling test designedto identifygenomic alterations within hundreds of cancer-related genes in hematologic malignancies, sarcomas,and pediatric cancers. PPAATIENTTIENT Biomarker Findings DISEASE Soft tissue sarcoma (NOS) MicrMicrosatosatellitellite statuse status -- MSI-High NAME TTumorumor Mutational BurBurdenden -- TMB-High (40 Muts/Mb) DATE OF BIRTH SEX Genomic Findings For a complete list of the genes assayed, please refer to the Appendix. MEDICAL RECORD # NTRK1NTRK1 A10A107V7V - subclonal, JJAK2AK2 amplification - equivequivocalocal†† PHYPHYSICIANSICIAN †† rrearrearrangangementement intrintron 6on 6 KDM4CKDM4C amplification ORDERING PHYSICIAN CD2CD2774 (PD-L1)4 (PD-L1) amplification MITFMITF amplification MEDICAL FACILITY †† EEGFRGFR amplification - equivequivocalocal NONOTTCH1CH1 D18D18770N0N ADDITIONAL RECIPIENT PDCD1LPDCD1LG2G2 (PD-L2) amplification PPAX5AX5 loslosss MEDICAL FACILITY ID AATRXTRX T158T1582f2fs*2s*244 PPCLCLOO A915S - subclonal†† PATHOLOGIST CCADAD V12V12226I6I PRKDCPRKDC T12T12669M9M SPESPECIMENCIMEN CDKN2A/B loslosss PPTPN11TPN11 V428MV428M SPECIMEN SITE CCTNNA1TNNA1 R55R551Q1Q SMARSMARCCA4A4 G1232DG1232D SPECIMEN ID EPHA3EPHA3 amplification TP53TP53 R2R273H, R1773H, R175H5H SPECIMEN TYPE FFANCD2ANCD2 truncation intrintron 31on 31 ZMZMYYM3M3 rrearrearrangangement eement exxon 17on 17 DATE OF COLLECTION FFOOXP1XP1 G433*, amplification SPECIMEN RECEIVED † See About the Test in appendix for details. 1515 TTherherapieapiess with Clinical BeneBenefitfit 2244 Clinical TClinical Trialsrials 00 TTherherapieapiess with Lack oof Rf Reesponsesponse THERAPIES WITH CLINICAL BENEFIT THERAPIES WITH CLINICAL BENEFIT BIOMARKER FINDINGS (IN P(IN PAATIENT’TIENT’S TUS TUMORMOR TYPE) (IN O(IN OTHER TUTHER TUMORMOR TYPE) Microsatellite status - MSI-High Pembrolizumab Atezolizumab Avelumab Cemiplimab-rwlc Durvalumab 10 T10 Trialsrials see psee p..2277 Nivolumab Tumor Mutational Burden - TMB-High (40 none Atezolizumab Muts/Mb) SAMPLEAvelumab Cemiplimab-rwlc Durvalumab Nivolumab 10 T10 Trialsrials see psee p..2929 Pembrolizumab Electronically signed by Jo-Anne Vergilio, M.D. | Jeffrey Ross, M.D., Medical Director, , M.D. | | Sample AnalyAnalysis:sis:150 Second St., 1st Floor, Cambridge, MA 02141 ··CLIA: 22D2027531 Foundation Medicine, Inc. | 1.888.988.3639 Sample PSample Prrepareparaation:tion:7010 Kit Creek Road, Morrisville, NC 27560 ··CLIA: 34D2044309 PAGE 1 of 56 PATIENT TUMOR TYPE REPORT DATE TRF# ABOUT THE TESTESTT FoundationOne®Heme is a comprehensive genomic profiling test designedto identifygenomic alterations within hundreds of cancer-related genes in hematologic malignancies, sarcomas,and pediatric cancers. THERAPIES WITH CLINICAL BENEFIT THERAPIES WITH CLINICAL BENEFIT GENOMIC FINDINGS (IN P(IN PAATIENT’TIENT’S TUS TUMORMOR TYPE) (IN O(IN OTHER TUTHER TUMORMOR TYPE) NTRK1 - A107V - subclonal, rearrangement Larotrectinib Crizotinib intron 6 7 T7 Trialsrials see psee p..3434 CD274 (PD-L1) - amplification none Atezolizumab Avelumab Cemiplimab-rwlc Durvalumab Nivolumab 10 T10 Trialsrials see psee p..3131 Pembrolizumab EGFR - amplification - equivocal none Afatinib Cetuximab Dacomitinib Erlotinib Gefitinib Lapatinib 6 T6 Trialsrials see psee p..3333 Panitumumab PDCD1LG2 (PD-L2) - amplification none Atezolizumab Avelumab Cemiplimab-rwlc Durvalumab Nivolumab 10 T10 Trialsrials see psee p..3636 Pembrolizumab SAMPLE Electronically signed by Jo-Anne Vergilio, M.D. | Jeffrey Ross, M.D., Medical Director, , M.D. | 1 | Sample AnalyAnalysis:sis:150 Second St., 1st Floor, Cambridge, MA 02141 ··CLIA: 22D2027531 Foundation Medicine, Inc. | 1.888.988.3639 Sample PSample Prrepareparaation:tion:7010 Kit Creek Road, Morrisville, NC 27560 ··CLIA: 34D2044309 PAGE 2 of 56 PATIENT TUMOR TYPE REPORT DATE Soft tissue sarcoma (NOS) TRF# ABOUT THE TESTESTT FoundationOne®Heme is a comprehensive genomic profiling test designedto identifygenomic alterations within hundreds of cancer-related genes in hematologic malignancies, sarcomas,and pediatric cancers. GENOMIC FINDINGS WITH NO REPORTABLE THERAPEUTIC OR CLINICAL TRIALS OPTIONS For more information regarding biological and clinical significance, including prognostic, diagnostic, germline, and potential chemosensitivity implications, see the Genomic Findings section. AATRX -TRX - T1582fs*24 p. 8 MITF -MITF - amplification p. 12 CAD -CAD - V1226I p. 9 NONOTTCH1 -CH1 - D1870N p. 13 CDKN2A/B - loss p. 9 PPAX5 -AX5 - loss p. 13 CCTNNA1 -TNNA1 - R551Q p. 10 PPCLCLO -O - A915S - subclonal p. 14 EPHA3 -EPHA3 - amplification p. 10 PRKDC -PRKDC - T1269M p. 14 FFANCD2 -ANCD2 - truncation intron 31 p. 11 PPTPN11 -TPN11 - V428M p. 15 FFOOXP1 -XP1 - G433*, amplification p. 11 SMARSMARCA4 -CA4 - G1232D p. 15 JJAK2 -AK2 - amplification - equivocal p. 11 TP53 -TP53 - R273H, R175H p. 16 KDM4C -KDM4C - amplification p. 12 ZMZMYYM3 -M3 - rearrangement exon 17 p. 16 NONOTETE Genomic alterations detected may be associated with activity of certain FDA-approved drugs; however, the agents listed in this report may have varied clinical evidence in the patient's tumor type. Neither the therapeutic agents nor the trials identified are ranked in order of potential or predicted efficacy for this patient, nor are they ranked in order of level of evidence for this patient's tumor type. SAMPLE Electronically signed by Jo-Anne Vergilio, M.D. | Jeffrey Ross, M.D., Medical Director, , M.D. | | Sample AnalyAnalysis:sis:150 Second St., 1st Floor, Cambridge, MA 02141 ··CLIA: 22D2027531 Foundation Medicine, Inc. | 1.888.988.3639 Sample PSample Prrepareparaation:tion:7010 Kit Creek Road, Morrisville, NC 27560 ··CLIA: 34D2044309 PAGE 3 of 56 PATIENT TUMOR TYPE REPORT DATE Soft tissue sarcoma (NOS) TRF# BIOMARKER FINDINGFINDINGSS BIOMARKER tumor and normal sarcomas in the TCGA pathway proteins, primarily MLH1, MSH2, Microsatellite status dataset, of which 40% were leiomyosarcomas MSH6, or PMS2 20-22. This sample has a high and 25% were liposarcomas, only 0.8% (2/255) level of MSI, equivalent to the clinical CACATEGORTEGORYY of samples were MSI-high (MSI-H) 12. In definition of an MSI-high (MSI-H) tumor: one MSI-High smaller studies of soft tissue sarcoma, reports with mutations in >30% of microsatellite of MSI at any level have been rare, with the markers 23-25. MSI-H status indicates high-level highest incidences between 11% (2/18) to 25% deficiency in MMR and typically correlates POPOTENTIALTENTIAL TREATREATMENT STMENT STRATRATEGIESTEGIES (10/40) of cases 13-18. In one study, MSI was with loss of expression of at least one, and On the basis of prospective clinical evidence in reported to occur more frequently in high- often two, MMR family proteins 20,22,24-25. multiple solid tumor types, MSI and associated grade soft tissue sarcomas compared with While approximately 80% of MSI-H tumors increased mutational burden 1-2 may predict lower grade 19. However, the prognostic arise due to somatic inactivation of an MMR sensitivity to anti-PD-1 and anti-PD-L1 significance of MSI in sarcoma is unknown pathway protein, about 20% arise due to immune checkpoint inhibitors3-4 2,5-6, (PubMed, Jan 2018). germline mutations in one of the MMR genes including the approved therapies nivolumab7-8, 20, which are associated with a condition pembrolizumab 9-10, atezolizumab, avelumab, FINDING SUMMARSUMMARYY known as Lynch syndrome (also known as and durvalumab3-4 5. Microsatellite instability (MSI) is a condition of hereditary nonpolyposis colorectal cancer or 26 genetic hypermutability that generates HNPCC) . Lynch syndrome leads to an FREQUENCFREQUENCYY & PROGNOPROGNOSISSIS excessive amounts of short insertion/deletion increased risk of colorectal, endometrial, gastric, and other cancers 26-28 and has an Reports of MSI in sarcomas in the literature mutations in the genome; it generally occurs at estimated prevalence in the general population are conflicting and varied due to substantial microsatellite DNA sequences and is caused by ranging from 1:600 to 1:2000 29-31. Therefore, heterogeneity, lack of consensus on the a deficiency in DNA mismatch repair (MMR) in the appropriate clinical context, germline markers and methods used for MSI in the tumor 20. Defective MMR and testing of MLH1, MSH2, MSH6, and PMS2 is assessment, and small sample size in most consequent MSI occur as a result of genetic or recommended. studies 11. In a computational analysis of paired epigenetic inactivation of one of the MMR SAMPLE Electronically signed by Jo-Anne Vergilio, M.D. | Jeffrey Ross, M.D., Medical Director, , M.D. || Sample AnalyAnalysis:sis:150 Second St., 1st Floor, Cambridge, MA 02141 ··CLIA: 22D2027531 Foundation Medicine, Inc. | 1.888.988.3639 Sample PSample Prrepareparaation:tion:7010 Kit Creek Road, Morrisville, NC 27560 ··CLIA: 34D2044309 PAGE 4 of 56 PATIENT TUMOR TYPE REPORT DATE Soft tissue sarcoma (NOS) TRF# BIOMARKER FINDINGFINDINGSS BIOMARKER with pembrolizumab 38 or nivolumab 39, a peripheral nerve sheath tumor (MPNST) (8.2%) Tumor Mutational patient with hypermutant glioblastoma who having the highest percentage of cases with obtained clinical benefit from pembrolizumab high TMB (>20 muts/Mb)45. Increased Burden 40, 2 pediatric patients with biallelic mismatch mutation burden has been reported in CACATEGORTEGORYY repair deficiency-associated ultrahypermutant undifferentiated pleomorphic sarcomas as TMB-High (40 Muts/Mb) glioblastoma who experienced clinically and compared to Ewing sarcomas or radiologically significant
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