Final Report

Patient Specimen Information Ordered By

Name: NB, 11472/18 Primary Tumor Site: Breast, NOS Zoran Gatalica, MD
Date of Birth: 03/12/2019 Specimen Site: Cervical lymph node Caris Life Sciences - Consultation
Sex: Female Specimen ID: 11472/18-4 4610 South 44th Place
Case Number: TN19-108696 Specimen Collected: 12-Mar-2019 Phoenix, AZ 85040 USA
1 (800) 901-5177
Diagnosis: Carcinoma, NOS Completion of Testing: 10-May-2019

Results Summary
CANCER TYPE RELEVANT BIOMARKERS CANCER TYPE RELEVANT BIOMARKERS (cont)

Biomarker Method Result Biomarker Method Result

MSI NGS Stable ESR1 NGS Mutation Not Detected

NTRK1 RNA-Seq Fusion Not Detected Mutated, Pathogenic

PIK3CA NGS
NTRK2 RNA-Seq Fusion Not Detected Exon 21 | p.H1047R

NTRK3 RNA-Seq Fusion Not Detected PTEN NGS Mutation Not Detected

Tumor Mutational Burden Intermediate | 9 Mutations/Mb O T H E R F I N D I N G S (see page 2 for additional results)

AKT1 NGS Mutation Not Detected Biomarker Method Result

Mutated, Presumed Benign Mutated, Presumed Pathogenic

BRCA1 NGS CHEK2 NGS
Exon 5 | c.301+7G>A Exon 4 | p.I157T

BRCA2 NGS Mutation Not Detected Mutated, Pathogenic

TP53 NGS
NGS Mutation Not Detected Exon 5 | p.P142fs
ERBB2 (Her2/Neu)
CNA-NGS Amplified

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 Final Report

Biomarker Results
This summary includes biomarkers most commonly associated with cancer. Complete details of all biomarkers tested can be found in the Appendix.

GENOMIC SIGNATURES

Biomarker Method Result

Microsatellite Instability (MSI) NGS Stable

Result: Intermediate

Tumor Mutational Burden (TMB) NGS

9
Low 7 Intermediate 17 High

GENES TESTED WITH MUTATIONS/ALTERATIONS

Gene Method Variant Interpretation Protein Alteration Exon DNA Alteration Variant Frequency %

CHEK2 NGS Mutated, Presumed Pathogenic p.I157T 4 c.470T>C 16

ERBB2
CNA-NGS Amplified - - - -
(Her2/Neu)

PIK3CA NGS Mutated, Pathogenic p.H1047R 21 c.3140A>G 25

c.424 _426
TP53 NGS Mutated, Pathogenic p.P142fs 5 37
delinsAC

Unclassified alterations for DNA sequencing can be found in the Appendix.

Formal nucleotide nomenclature and gene reference sequences can be found in the Appendix of this report.

Other Findings
GENES TESTED WITH INDETERMINATE* RESULTS BY NGS

ARID1A ASXL1 DNMT3A FANCE FLT3 KDM5C KMT2D NF1 PMS2 PTCH1 TERT

* Genes in this table were ruled indeterminate due to low coverage for some or all exons. Please see Appendix for a complete list of indeterminate genes.

Additional results continued on the next page. >

PATIENT: NB, 11472/18 (12-MAR-2019) TN19-108696 PHYSICIAN: ZORAN GATALICA, MD

4610 South 44th Place, Suite 100 • Phoenix, AZ 85040 • (888) 979-8669 • Fax: (866) 479-4925
CLIA 03D1019490 • CAP 7195577 • ISO 15189:2012 • Zoran Gatalica, MD, DSc, Medical Director • ©2019 Caris Life Sciences. All rights reserved. Page 2 of 7
 Final Report

Other Findings
GENES TESTED WITHOUT POINT MUTATIONS OR INDELS BY NGS

ABL1 AKT1 ALK AMER1 AR ARAF ARID2 ATM ATR ATRX BAP1 BARD1

BCOR BLM BMPR1A BRAF BRCA2 BRIP1 CCND1 CCND2 CCND3 CD79B CDC73 CDH1

CDK12 CDK4 CDK6 CDKN1B CDKN2A CHEK1 CIC CREBBP CSF1R CTNNB1 CYLD DDR2

ERBB2
DICER1 EGFR EP300 (Her2/ ERBB4 ERCC2 ESR1 EZH2 FANCA FANCC FANCD2 FANCF
Neu)

FANCG FANCL FBXW7 FGFR1 FGFR2 FGFR3 FGFR4 FH FLCN FLT1 FLT4 FOXL2

FUBP1 GATA3 GNA11 GNA13 GNAQ GNAS H3F3A H3F3B HIST1H3B HNF1A HRAS IDH1

KDR
IDH2 IRF4 JAK1 JAK2 JAK3 KDM6A KIT KMT2A KMT2C KRAS LCK
(VEGFR2)

MAP2K1 MAP2K2
MAX MEN1 MET MITF MLH1 MPL MRE11 MSH2 MSH6 MTOR
(MEK1) (MEK2)

MUTYH MYCN MYD88 NBN NF2 NOTCH1 NPM1 NRAS NTRK1 NTRK2 NTRK3 PALB2

PBRM1 PDGFRA PDGFRB PHOX2B PIK3R1 PIM1 PMS1 POLE POT1 PPARG PPP2R1A PRDM1

PRKAR1A PRKDC PTEN PTPN11 RAD50 RAF1 RB1 RET RNF43 SDHAF2 SDHB SDHC

SDHD SETD2 SF3B1 SMAD2 SMAD4 SMARCA4 SMARCB1 SMARCE1 SMO SPOP SRC STK11

SUFU TSC1 TSC2 U2AF1 VHL WRN WT1

GENES TESTED WITH NO AMPLIFICATION DETECTED BY NGS

CD274
AKT2 ALK ARID1A AURKB CCND1 CCND3 CCNE1 CDK4 CDK6 CDK8 CDKN2A
(PD-L1)

KDR MAP2K1
CREBBP CRKL EGFR EP300 EZH2 FGF10 FGFR1 FGFR2 FGFR3 GATA3
(VEGFR2) (MEK1)

MCL1 MDM2 MET MYC NF2 NFKBIA NTRK1 RB1 RICTOR ROS1 TOP1 WT1

Additional results continued on the next page. >

PATIENT: NB, 11472/18 (12-MAR-2019) TN19-108696 PHYSICIAN: ZORAN GATALICA, MD

4610 South 44th Place, Suite 100 • Phoenix, AZ 85040 • (888) 979-8669 • Fax: (866) 479-4925
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 Final Report

Other Findings
GENES TESTED WITH NO RNA ALTERATIONS BY NGS

Fusion Not Detected

ABL1 AKT3 ALK ARHGAP26 AXL BCR BRAF BRD3 BRD4 EGFR ERG ESR1

ETV1 ETV4 ETV5 ETV6 EWSR1 FGFR1 FGFR2 FGFR3 FGR INSR MAML2 MAST1

MAST2 MET MSMB MUSK MYB NOTCH1 NOTCH2 NRG1 NTRK1 NTRK2 NTRK3 NUMBL

NUTM1 PDGFRA PDGFRB PIK3CA PKN1 PPARG PRKCA PRKCB RAF1 RELA RET ROS1

RSPO2 RSPO3 TERT TFE3 TFEB THADA TMPRSS2

Variant Transcript Not Detected

AR EGFRvIII MET

The complete list of unclassified alterations for RNA Whole Transcriptome Sequencing are available by request.

PATIENT: NB, 11472/18 (12-MAR-2019) TN19-108696 PHYSICIAN: ZORAN GATALICA, MD

4610 South 44th Place, Suite 100 • Phoenix, AZ 85040 • (888) 979-8669 • Fax: (866) 479-4925
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 Final Report

Notes of Significance
SEE APPENDIX FOR DETAILS

Clinical Trials Connector TM opportunities based on biomarker expression: 2 Chemotherapy Trials | 4 Targeted Therapy Trials. See page 6 for
details.

Specimen Information
Specimen ID: 11472/18-4 Specimen Collected: 03/12/2019

Specimen Received: 03/12/2019 Testing Initiated: 04/22/2019

Gross Description: 1 (A) Paraffin Block - Client ID(11472/18-4) 1 (B) Tissue Biopsy Slide stained - Client ID(11472/18-4) 1 (C) Tissue Biopsy Slide stained -
Client ID(11472/18B).

Dissection Information: A laboratory technician harvested targeted tissues for extraction from the marked areas using a dissection microscope. The
areas marked and extracted were microscopically reexamined on post-scraped slides and adequacy of scraping was reviewed by a board certified
Pathologist.

PATIENT: NB, 11472/18 (12-MAR-2019) TN19-108696 PHYSICIAN: ZORAN GATALICA, MD

4610 South 44th Place, Suite 100 • Phoenix, AZ 85040 • (888) 979-8669 • Fax: (866) 479-4925
CLIA 03D1019490 • CAP 7195577 • ISO 15189:2012 • Zoran Gatalica, MD, DSc, Medical Director • ©2019 Caris Life Sciences. All rights reserved. Page 5 of 7
 Final Report

Clinical Trials Connector TM

For a complete list of open, enrolling clinical trials visit MI Portal to access the Clinical Trials Connector . This personalized, real-time web-based
service provides additional clinical trial information and enhanced searching capabilities, including, but not limited to:
• Location: filter by geographic area
• Biomarker(s): identify specific biomarkers associated with open clinical trials to choose from
• Drug(s): search for specific therapies
• Trial Sponsor: locate trials based on the organization supporting the trial(s)
Visit www.CarisMolecularIntelligence.com to view all matched trials. Therapeutic agents listed below may or may not be currently FDA
approved for the tumor type tested.

CHEMOTHERAPY CLINICAL TRIALS (2)

Drug Class Biomarker Method Investigational Agent(s)

Platinum compounds (2) CHEK2 NGS carboplatin

TARGETED THERAPY CLINICAL TRIALS (4)

Drug Class Biomarker Method Investigational Agent(s)

HER2-targeted therapy (2) ERBB2 (Her2/Neu) CNA-NGS trastuzumab

PI3K/Akt/mTor inhibitors (2) PIK3CA NGS everolimus, sirolimus, temsirolimus

( ) = represents the total number of clinical trials identified by the Clinical Trials Connector for the provided drug class or table.

Please refer to the "Notes of Significance" section that may contain additional information regarding therapy associations.

PATIENT: NB, 11472/18 (12-MAR-2019) TN19-108696 PHYSICIAN: ZORAN GATALICA, MD

4610 South 44th Place, Suite 100 • Phoenix, AZ 85040 • (888) 979-8669 • Fax: (866) 479-4925
CLIA 03D1019490 • CAP 7195577 • ISO 15189:2012 • Zoran Gatalica, MD, DSc, Medical Director • ©2019 Caris Life Sciences. All rights reserved. Page 6 of 7
 Final Report

Disclaimer
Decisions regarding care and treatment should not be solely based on a single test such as this test or the information contained in this report. The
decision to select any, all, or none of the listed therapies resides within the discretion of the treating physician. Decisions on patient care and treatment
must be based on the independent medical judgment of the treating physician, taking into consideration all applicable information concerning the
patient’s condition, including but not limited to, patient and family history, physical examinations, information from other diagnostic tests, and patient
preferences, in accordance with the applicable standard of care.

Individual assays that are available through Caris Molecular Intelligence® include both Laboratory Developed Tests (LDT) and U.S. Food and Drug
Administration (FDA) approved or cleared tests. Caris MPI, Inc. d/b/a Caris Life Sciences® is certified under the Clinical Laboratory Improvement
Amendments of 1988 (CLIA-88) as qualified to perform high complexity clinical laboratory testing, including all of the assays that comprise the Caris
Molecular Intelligence®. Caris has validated the LDTs and their test performance characteristics were determined by Caris pursuant to CLIA-88 and
accompanying regulations. Caris’ CLIA certification number is located at the bottom of each page of this report. Tests have not all been cleared or
approved by the FDA. The FDA has determined that clearance or approval is not necessary for certain laboratory developed tests. These tests are used
for clinical purposes. They should not be regarded as investigational or for research.

This report includes information about therapies that may be associated with clinical benefit based on Caris Life Sciences’ review of the NCCN
Compendium® guidelines, relevance of tumor lineage, level of published evidence and strength of biomarker results. Associated therapies may or may
not be suitable for administration to a particular patient.

Drug associations provided in this report do not guarantee that any particular agent will be effective with the treatment of any particular condition.
Caris Life Sciences expressly disclaims and makes no representation or warranty whatsoever relating, directly or indirectly, to the conclusions drawn from
its review of scientific literature, including information and conclusions relating to therapies that are included or omitted from this report. There is no
guarantee that any third party will provide reimbursement for any of the tests performed or any treatment decision made based on the results.

The information presented in the Clinical Trials Connector™ section of this report, if applicable, is compiled from sources believed to be reliable and
current. However, the accuracy and completeness of the information provided herein cannot be guaranteed. The clinical trials information present in the
biomarker description was compiled from www.clinicaltrials.gov. The contents are to be used only as a guide, and health care providers should employ
their best comprehensive judgment in interpreting this information for a particular patient. Specific eligibility criteria for each clinical trial should be
reviewed as additional inclusion criteria may apply.

Caris Molecular Intelligence is subject to Caris’ intellectual property. Patent www.carislifesciences.com/ip.

Electronic Signature
Zoran Gatalica, MD
05/10/2019

PATIENT: NB, 11472/18 (12-MAR-2019) TN19-108696 PHYSICIAN: ZORAN GATALICA, MD

4610 South 44th Place, Suite 100 • Phoenix, AZ 85040 • (888) 979-8669 • Fax: (866) 479-4925
CLIA 03D1019490 • CAP 7195577 • ISO 15189:2012 • Zoran Gatalica, MD, DSc, Medical Director • ©2019 Caris Life Sciences. All rights reserved. Page 7 of 7
 Final Report

Mutational Analysis by Next-Generation Sequencing (NGS)

TUMOR MUTATIONAL BURDEN

Mutations / Megabase Result

9 Intermediate

TMB Methods
Tumor Mutational Burden was performed based on Next Generation Sequencing (NGS) analysis from genomic DNA isolated from a formalin-fixed
paraffin-embedded tumor sample using the Illumina NextSeq platform. NGS was developed and its performance characteristics determined by Caris
Life Sciences.
Tumor Mutational Burden is calculated using only missense mutations that have not been previously reported as germline alterations. A high
mutational burden is a potential indicator of immunotherapy response (Le et al., NEJM, 2015; Rizvi et al., Science, 2015; Rosenberg et al., Lancet, 2016;
Snyder et al., NEJM, 2014). Caris Life Sciences has defined threshold levels for Tumor Mutational Burden and establish cutoff points based on published
evidence and internal data/experience:
●
High: greater than or equal to 17 mutations/Megabase (≥17 mutations/Mb). Approximately 7% of Caris Molecular Intelligence cases reported a
High result.
●
Intermediate: greater than or equal to 7 but fewer than 17 mutations/ Megabase (≥7 and <17 mutations/Mb). Approximately 34% of Caris
Molecular Intelligence cases reported an Intermediate result.
●
Low: less than or equal to 6 mutations/Megabase (≤6 mutations/Mb). Approximately 59% of Caris Molecular Intelligence cases reported a Low
result.

MICROSATELLITE INSTABILITY ANALYSIS

Test Interpretation Result

No microsatellite instability detected Stable

MSI
Procedure: NGS

Microsatellite Instability Analysis

Microsatellite instability status by NGS (MSI-NGS) is measured by the direct analysis of known microsatellite regions sequenced in the CMI 592 gene panel.
To establish clinical thresholds, MSI-NGS results were compared with results from over 2,000 matching clinical cases analyzed with traditional, PCR-based
methods. Genomic variants in the microsatellite loci are detected using the same depth and frequency criteria as used for mutation detection. Only
insertions and deletions resulting in a change in the number of tandem repeats are considered in this assay. Some microsatellite regions with known
polymorphisms or technical sequencing issues are excluded from the analysis. The total number of microsatellite alterations in each sample are counted
and grouped into three categories: High, Equivocal and Stable. MSI-Low results are reported in the Stable category. Equivocal results have a total number
of microsatellite alterations in between High and Stable.

Additional Next-Generation Sequencing results continued on the next page. >

PATIENT: NB, 11472/18 (12-MAR-2019) TN19-108696 PHYSICIAN: ZORAN GATALICA, MD

4610 South 44th Place, Suite 100 • Phoenix, AZ 85040 • (888) 979-8669 • Fax: (866) 479-4925
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 Final Report

Mutational Analysis by Next-Generation Sequencing (NGS)

GENES TESTED WITH ALTERATIONS

Gene Variant Interpretation Protein Alteration Exon DNA Alteration Variant Frequency % Transcript ID

CHEK2 Mutated, Presumed Pathogenic p.I157T 4 c.470T>C 16 NM_007194

Interpretation: This CHEK2 variant is carried by approximately 1% of European individuals. It is reported to be associated with a slightly increased risk
of various tumor types (Cybulski 2004 Am J Hum Genet 75:1131; Han 2013 DNA Cell Biol 32:329).

The CHEK2 gene encodes a protein Chek2 (Checkpoint kinase 2) that is involved in the initiation of cell cycle arrest and DNA repair following the detection of DNA damage,
in particular, double strand breaks. Chek2 stabilizes p53, leading to cell cycle arrest in G1, and activates BRCA1, facilitating DNA repair. Mutations or deletions in CHEK2
have been associated with colon, prostate, breast, pancreas and ovarian cancers.

PIK3CA Mutated, Pathogenic p.H1047R 21 c.3140A>G 25 NM_006218

Interpretation: The common oncogenic p.H1047R mutation was detected in PIK3CA (Burke 2012 Proc Natl Acad Sci USA 109:15259)

PIK3CA or phosphoinositide-3-kinase catalytic alpha polypeptide encodes a protein in the PI3 kinase pathway. This pathway is an active target for drug development.
PIK3CA somatic mutations have been found in breast (26%), endometrial (23%), urinary tract (19%), colon (13%), and ovarian (11%) cancers. Somatic mosaic activating
mutations in PIK3CA are said to cause CLOVES syndrome.

TP53 Mutated, Pathogenic p.P142fs 5 c.424 _426 delinsAC 37 NM_000546

Interpretation: A pathogenic frameshift mutation was detected in TP53

TP53, or p53, plays a central role in modulating response to cellular stress through transcriptional regulation of genes involved in cell-cycle arrest, DNA repair, apoptosis,
and senescence. Inactivation of the p53 pathway is essential for the formation of the majority of human tumors. Mutation in p53 (TP53) remains one of the most commonly
described genetic events in human neoplasia, estimated to occur in 30-50% of all cancers. Generally, presence of a disruptive p53 mutation is associated with a poor
prognosis in all types of cancers, and diminished sensitivity to radiation and chemotherapy. Germline p53 mutations are associated with the Li-Fraumeni syndrome (LFS)
which may lead to early-onset of several forms of cancer currently known to occur in the syndrome, including sarcomas of the bone and soft tissues, carcinomas of the
breast and adrenal cortex (hereditary adrenocortical carcinoma), brain tumors and acute leukemias.

The next-generation sequencing assay performed by Caris Life Sciences examines nucleic acids obtained from tumor tissue only and does not examine
normal tissue such as tumor adjacent tissue or whole or peripheral blood. As such, the origin of any mutation detected may be a somatic mutation
(not inherited) or a germline mutation (inherited) and will not be distinguishable by this assay. It is recommended that results be considered within the
patient’s clinical and health history. If a germline inheritance pattern is suspected then counseling by a board certified genetic counselor is recommended.

GENES TESTED WITH UNCLASSIFIED MUTATIONS*

Gene Protein Alteration Exon DNA Alteration Variant Frequency % Transcript ID

APC p.R1146C 16 c.3436C>T 27 NM_000038

BRCA1 c.301+7G>A 5 c.301+7G>A 30 NM_007294

CARD11 p.D1152N 25 c.3454G>A 71 NM_032415

EBF1 p.R311H 10 c.932G>A 62 NM_024007

EPHA3 p.F801Y 14 c.2402T>A 35 NM_005233

ERBB3 p.R1202W 28 c.3604C>T 18 NM_001982

MKL1 p.R515W 12 c.1543C>T 65 NM_020831

Additional Next-Generation Sequencing results continued on the next page. >

PATIENT: NB, 11472/18 (12-MAR-2019) TN19-108696 PHYSICIAN: ZORAN GATALICA, MD

4610 South 44th Place, Suite 100 • Phoenix, AZ 85040 • (888) 979-8669 • Fax: (866) 479-4925
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 Final Report

Mutational Analysis by Next-Generation Sequencing (NGS)

GENES TESTED WITH UNCLASSIFIED MUTATIONS*

Gene Protein Alteration Exon DNA Alteration Variant Frequency % Transcript ID

MYH11 p.Q1360H 30 c.4080G>C 14 NM_002474

NSD1 p.D1428Y 8 c.4282G>T 10 NM_022455

NSD1 p.L1573F 12 c.4719G>C 10 NM_022455

NSD1 p.R1578T 12 c.4733G>C 11 NM_022455

PBX1 p.Q156H 3 c.468G>C 22 NM_002585

RNF213 p.P2274L 29 c.6821C>T 69 NM_001256071

ROS1 p.G365A 10 c.1094G>C 49 NM_002944

ZBTB16 p.G313C 2 c.937G>T 10 NM_006006

* Any mutations in the above genes that are known by Caris to be clinically significant (i.e., pathogenic or presumed pathogenic) are reported with interpretation in the
body of the report. Any remaining mutations are listed above and have not been classified by Caris.

Additional Next-Generation Sequencing results continued on the next page. >

PATIENT: NB, 11472/18 (12-MAR-2019) TN19-108696 PHYSICIAN: ZORAN GATALICA, MD

4610 South 44th Place, Suite 100 • Phoenix, AZ 85040 • (888) 979-8669 • Fax: (866) 479-4925
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 Final Report

Mutational Analysis by Next-Generation Sequencing (NGS)

COMPLETE LIST OF GENES TESTED WITH INDETERMINATE* RESULTS

ADGRA2 CCNE1 FGF3 KIAA1549 NIN RUNX1

ARID1A CD74 FGF4 KMT2D NKX2-1 STAT5B

ASPSCR1 CD79A FGFR1OP LYL1 NOTCH2 TAF15

ASXL1 CEBPA FLI1 MALT1 NUTM2B TAL1

AXIN1 COL1A1 FLT3 MAP3K1 PCSK7 TCF3

AXL DNMT3A FNBP1 MED12 PER1 TERT

BCL11A DOT1L FOXO1 MEF2B PIK3R2 TPM4

BRD3 ELL FSTL3 MLLT1 PMS2 VEGFB

BRD4 ELN FUS MLLT6 PRDM16

BUB1B EPS15 HIP1 MNX1 PTCH1

CACNA1D ETV4 HOXA13 MUC1 RAC1

CBFA2T3 FANCE HOXD11 NF1 RALGDS

CCDC6 FEV KDM5C NFKB2 RMI2

* Genes in this table were ruled indeterminate due to low coverage for some or all exons.

GENES TESTED WITH NO MUTATIONS DETECTED

ABL1 BRAF CIC FANCC FUBP1 JAK2

AKT1 BRCA2 CREBBP FANCD2 GATA3 JAK3

ALK BRIP1 CSF1R FANCF GNA11 KDM6A

AMER1 CCND1 CTNNB1 FANCG GNA13 KDR (VEGFR2)

AR CCND2 CYLD FANCL GNAQ KIT

ARAF CCND3 DDR2 FBXW7 GNAS KMT2A

ARID2 CD79B DICER1 FGFR1 H3F3A KMT2C

ATM CDC73 EGFR FGFR2 H3F3B KRAS

ATR CDH1 EP300 FGFR3 HIST1H3B LCK

ATRX CDK12 ERBB2 (Her2/Neu) FGFR4 HNF1A MAP2K1 (MEK1)

BAP1 CDK4 ERBB4 FH HRAS MAP2K2 (MEK2)

BARD1 CDK6 ERCC2 FLCN IDH1 MAX

BCOR CDKN1B ESR1 FLT1 IDH2 MEN1

BLM CDKN2A EZH2 FLT4 IRF4 MET

BMPR1A CHEK1 FANCA FOXL2 JAK1 MITF

Additional Next-Generation Sequencing results continued on the next page. >

PATIENT: NB, 11472/18 (12-MAR-2019) TN19-108696 PHYSICIAN: ZORAN GATALICA, MD

4610 South 44th Place, Suite 100 • Phoenix, AZ 85040 • (888) 979-8669 • Fax: (866) 479-4925
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 Final Report

Mutational Analysis by Next-Generation Sequencing (NGS)

GENES TESTED WITH NO MUTATIONS DETECTED

MLH1 NOTCH1 PIK3R1 PTPN11 SF3B1 TSC1

MPL NPM1 PIM1 RAD50 SMAD2 TSC2

MRE11 NRAS PMS1 RAF1 SMAD4 U2AF1

MSH2 NTRK1 POLE RB1 SMARCA4 VHL

MSH6 NTRK2 POT1 RET SMARCB1 WRN

MTOR NTRK3 PPARG RNF43 SMARCE1 WT1

MUTYH PALB2 PPP2R1A SDHAF2 SMO

MYCN PBRM1 PRDM1 SDHB SPOP

MYD88 PDGFRA PRKAR1A SDHC SRC

NBN PDGFRB PRKDC SDHD STK11

NF2 PHOX2B PTEN SETD2 SUFU

For a complete list of genes tested, visit www.CarisMolecularIntelligence.com/profilemenu.

NGS Methods
Next Generation Sequencing: Direct sequence analysis was performed on genomic DNA isolated from a formalin-fixed paraffin-embedded tumor
sample using the Illumina NextSeq platform. An Agilent customdesigned SureSelect XT assay was used to enrich 592 whole-gene targets. The genes
and amino acids evaluated in this report can be found at www.carislifesciences.com. All variants reported by this assay are detected with > 99%
confidence based on the frequency of the mutation present and the amplicon coverage. This test is not designed to distinguish between germ line
inheritance of a variant or acquired somatic mutation. This test has a sensitivity to detect as low as approximately 10% population of cells containing
a mutation with an analytic sensitivity of 96.9% to detect variants with frequency greater than 5%. This may not detect insertion/deletions events that
are larger than 44 bases. The Laboratory Developed Tests (LDT) Next Generation Sequencing (NGS) assays were developed and their performance
characteristics determined by Caris Life Sciences. These tests have not been cleared or approved by the US Food and Drug Administration. FDA
clearance or approval is not currently necessary. All performance characteristics were determined by Caris Life Sciences. Benign and non-coding
variants are not included in this report but are available upon request.
The versioned reference identifier used for the transcript ID was Feb.2009 (GRCh37/hg19).

PATIENT: NB, 11472/18 (12-MAR-2019) TN19-108696 PHYSICIAN: ZORAN GATALICA, MD

4610 South 44th Place, Suite 100 • Phoenix, AZ 85040 • (888) 979-8669 • Fax: (866) 479-4925
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 Final Report

Copy Number Alterations by Next-Generation Sequencing (NGS)

GENES TESTED WITH AMPLIFICATION DETECTED

ERBB2 (Her2/Neu)

GENES TESTED WITH NO AMPLIFICATION DETECTED

AKT2 CCNE1 CREBBP FGFR1 MCL1 NTRK1

ALK CD274 (PD-L1) CRKL FGFR2 MDM2 RB1

ARID1A CDK4 EGFR FGFR3 MET RICTOR

AURKB CDK6 EP300 GATA3 MYC ROS1

CCND1 CDK8 EZH2 KDR (VEGFR2) NF2 TOP1

CCND3 CDKN2A FGF10 MAP2K1 (MEK1) NFKBIA WT1

The CNA results reported in the table below have been assessed for general quality but have not been evaluated by a board-certified molecular
geneticist or evaluated for clinical significance. They are reported for informational purposes only.

GENES TESTED WITH UNEVALUATED AMPLIFICATION DETECTED

CLTC SUZ12

COMPLETE LIST OF GENES WITH INDETERMINATE CNA RESULTS

ADGRA2 FOXO1 MAP3K1 PRDM16 TCF3

FGF3 FUS MEF2B RALGDS TP53

FGF4 KMT2D PER1 STAT5B

CNA Methods
The copy number alteration (CNA) of each exon is determined by a calculation using the average sequencing depth of the sample along with the
sequencing depth of each exon and comparing this calculated result to a pre-calibrated value. If all exons within the gene of interest have an average
of ≥3 copies and the average copy number of the entire gene is ≥6 copies, the gene result is reported as amplified. If an average of ≥ 4, but < 6 copies
of a gene are detected, or if the average copy number of the gene is ≥6 copies, but contains exons with an average of < 3 copies, the gene result is
reported as intermediate. If an average of < 4 copies of a gene are detected, the gene result is reported as no amplification detected. A complete list of
copy number alteration genes are available upon request.

PATIENT: NB, 11472/18 (12-MAR-2019) TN19-108696 PHYSICIAN: ZORAN GATALICA, MD

4610 South 44th Place, Suite 100 • Phoenix, AZ 85040 • (888) 979-8669 • Fax: (866) 479-4925
CLIA 03D1019490 • CAP 7195577 • ISO 15189:2012 • Zoran Gatalica, MD, DSc, Medical Director • ©2019 Caris Life Sciences. All rights reserved. Appendix 6 of 7
 Final Report

Gene Fusion and Transcript Variant Detection by RNA Sequencing

GENES TESTED WITH NO GENE FUSION OR TRANSCRIPT VARIANT DETECTED

Fusion Not Detected

ABL1 AKT3 ALK ARHGAP26 AXL BCR BRAF BRD3 BRD4 EGFR ERG ESR1

ETV1 ETV4 ETV5 ETV6 EWSR1 FGFR1 FGFR2 FGFR3 FGR INSR MAML2 MAST1

MAST2 MET MSMB MUSK MYB NOTCH1 NOTCH2 NRG1 NTRK1 NTRK2 NTRK3 NUMBL

NUTM1 PDGFRA PDGFRB PIK3CA PKN1 PPARG PRKCA PRKCB RAF1 RELA RET ROS1

RSPO2 RSPO3 TERT TFE3 TFEB THADA TMPRSS2

Variant Transcript Not Detected

AR EGFRvIII MET

GENES TESTED WITH UNCLASSIFIED GENE FUSION OR TRANSCRIPT VARIANT DETECTED

Biomarker Fusion/Isoform Splice Site Transcript ID

RARA RARA:PSMD11 exon 1:exon 9 NM_001145302.2/NM_001270482.1

RARA RARA:PSMD11 exon 1:exon 8 NM_001145302.2/NM_001270482.1

RARA RARA:PSMD11 exon 1:exon 9 NM_000964.3/NM_001270482.1

RARA RARA:PSMD11 exon 1:exon 9 NM_001145302.2/NM_001270482.1

RARA RARA:PSMD11 exon 1:exon 8 NM_000964.3/NM_001270482.1

Gene Fusion Methods

Gene fusion and variant transcript detection were performed on mRNA isolated from a formalin-fixed paraffin-embedded tumor sample using the
Agilent SureSelectXT Low Input Library prep chemistry, optimized for FFPE tissue, in conjunction with the SureSelect Human All Exon V7 bait panel
(48.2 Mb) and the Illumina NovaSeq. This assay is designed to detect fusions occurring at known and novel breakpoints within genes. Only a portion
of genes tested are included in this report. The genes included in this report represent the subset of genes most commonly associated with cancer.
All results can be provided by request. Analytical validation of this test demonstrated ≥97% Positive Percent Agreement (PPA), ≥99% Negative Percent
Agreement (NPA) and ≥99% Overall Percent Agreement (OPA) with a validated comparator method.
The versioned reference identifier used for the transcript ID was Feb.2009 (GRCh37/hg19).
The complete list of unclassified alterations for RNA Whole Transcriptome Sequencing are available by request.

PATIENT: NB, 11472/18 (12-MAR-2019) TN19-108696 PHYSICIAN: ZORAN GATALICA, MD

4610 South 44th Place, Suite 100 • Phoenix, AZ 85040 • (888) 979-8669 • Fax: (866) 479-4925
CLIA 03D1019490 • CAP 7195577 • ISO 15189:2012 • Zoran Gatalica, MD, DSc, Medical Director • ©2019 Caris Life Sciences. All rights reserved. Appendix 7 of 7