• Test Code:
    5441
  • Department:
    Solid Tumors
  • Test Synonyms:
    Solid Tumor Panel Version 3Fusion geneGene fusionALKROS1NTRKACVR1AKT1AKT2AKT3ALKAMER1APCAPLNRARARAFARID1AARID2ASF1AATMATRATRXAURKAAXIN1B2MBAP1BARD1BRAFBRCA1BRCA2BRD4BRIP1BUB1BEMSYCASP8CCND1CCND2CCND3CCNE1CD274 (PD-L1)CDH1CDK12CDK4CDK6CDKN1BCDKN2ACHD4CHEK1CHEK2CICCOL2A1CTNNB1DDR2DDX11DDX3XDICER1EGFREGLN1EGLN2EIF1AXEPAS1ERBB2ERBB3ERBB4ERCC2ERCC3ERCC5ESR1FAM175AFANCAFANCCFANCD2FANCEFANCFFANCGFANCMFBXW7FGF19FGF3FGF4FGFR1FGFR2FGFR3FGFR4FHFUBP1GATA3GNA11GNAQGNASH3F3AHIST1H3BHIST1H3CHLA-AHLA-BHLA-CHOXB13HRASIDH1IDH2IDO1IDO2IFNGR1IFNGR2INPP4BIRF1JAK1JAK2KDRKEAP1KIF1BKITKLF4KRASLZTR1MAP2K1 (MEK1)MAP2K2 (MEK2)MAP2K4MAP3K1MAPK1MAXMC1RMDC1MDH2MDM2MDM4MEN1METMLH1MLH3MRE11AMSH2MSH3MSH6MTAPMTORMUTYHMYCMYCNMYOD1NBNNDUFAB1NF1NF2NRASNTRK1NTRK2NTRK3PALB2PBRM1PDCD1LG2PDGFRAPIK3CAPIK3CBPIK3R1PLAG1PLCG1PMS1PMS2POLEPPM1DPPP2R1APPP6CPRKAR1APRKCAPSMB5PTCH1PTENPTPN11PTPRBRAC1RAD50RAD51RAD51BRAD51CRAD51DRAD52RAD54LRAF1RASA1RB1RECQLRETREV7RHEBRICTORRINT1RIT1RNF139RNF43ROS1RPTORRRASSDHASDHAF1SDHAF2SDHAF3SDHAF4SDHBSDHCSDHDSETD2SF3B1SMAD4SMARCA2SMARCA4SMARCB1SMARCE1SMOSOCS1SPENSPOPSTAG2STAT3STK11SUFUTAP1TAP2TAPBPTCEB1TERTTMEM127TP53TP53BP1TRAF7TSC1TSC2VHLXRCC1YAP1YES1
  • CPT Code(s):
    81455
Background:

Features included:

  • Tumor mutation burden estimate (TMB)
  • Identification of microsatellite instability (MSI)
  • Genes related to resistance to immune checkpoint inhibitor treatment (HLA genes, B2M, JAK1, JAK2, IFNGR1, IFGR2)
  • GeneTrails® Solid Tumor Fusion Gene panel (RNA sequencing panel)

The GeneTrails© Comprehensive Solid Tumor Panel (CSTP) is a next-generation sequencing (NGS) test comprised of two amplicon-based libraries (one DNA, one RNA/cDNA) used to screen for clinically informative gene alterations that are important in making therapeutic decisions, including SNVs, in/dels, copy number alterations and gene fusion events. The test can detect microsatellite instability and provides an estimate of tumor mutation burden (TMB). CSTP is intended for the analysis of solid tumors from patients with clinically advanced disease (stage III or IV). It covers genes that are informative for the use of FDA-approved therapies in non-small cell lung cancer (EGFR, BRAF, ALK, ROS1), colorectal cancer (KRAS, NRAS, BRAF), breast cancer (PIK3CA), and bladder cancer (FGFR2/3). In addition, it can be used to select therapies that have pan-cancer approval (pembrolizumab for MSI-high, larotrectinib and entrectinib for NTRK gene fusions).

The partner-agnostic RNA gene fusion panel that is part of the CSTP encompasses all fusions for which FDA-approved therapies are available, as well as targets for ongoing clinical trials. The DNA panel includes genes recently linked to immuno-therapy resistance (HLA, B2M, TAP, TAPBP, JAK1, IFNGR1, IFGR2).

The GeneTrails© Comprehensive Solid Tumor Panel has national coverage for qualifying Medicare and Medicare Advantage patients across all solid tumors.

Gene List:

ACVR1

CCND1

ERCC2

HLA-A

MDC1

PDGFRA

RB1

SOCS1

AKT1

CCND2

ERCC3

HLA-B

MDH2

PIK3CA

RECQL

SPEN

AKT2

CCND3

ERCC5

HLA-C

MDM2

PIK3CB

RET

SPOP

AKT3

CCNE1

ESR1

HOXB13

MDM4

PIK3R1

REV7

STAG2

ALK

CD274 (PD-L1)

FAM175A

HRAS

MEN1

PLAG1

RHEB

STAT3

AMER1

CDH1

FANCA

IDH1

MET

PLCG1

RICTOR

STK11

APC

CDK12

FANCC

IDH2

MLH1

PMS1

RINT1

SUFU

APLNR

CDK4

FANCD2

IDO1

MLH3

PMS2

RIT1

TAP1

AR

CDK6

FANCE

IDO2

MRE11A

POLE

RNF139

TAP2

ARAF

CDKN1B

FANCF

IFNGR1

MSH2

PPM1D

RNF43

TAPBP

ARID1A

CDKN2A

FANCG

IFNGR2

MSH3

PPP2R1A

ROS1

TCEB1

ARID2

CHD4

FANCM

INPP4B

MSH6

PPP6C

RPTOR

TERT

ASF1A

CHEK1

FBXW7

IRF1

MTAP

PRKAR1A

RRAS

TMEM127

ATM

CHEK2

FGF19

JAK1

MTOR

PRKCA

SDHA

TP53

ATR

CIC

FGF3

JAK2

MUTYH

PSMB5

SDHAF1

TP53BP1

ATRX

COL2A1

FGF4

KDR

MYC

PTCH1

SDHAF2

TRAF7

AURKA

CTNNB1

FGFR1

KEAP1

MYCN

PTEN

SDHAF3

TSC1

AXIN1

DDR2

FGFR2

KIF1B

MYOD1

PTPN11

SDHAF4

TSC2

B2M

DDX11

FGFR3

KIT

NBN

PTPRB

SDHB

VHL

BAP1

DDX3X

FGFR4

KLF4

NDUFAB1

RAC1

SDHC

XRCC1

BARD1

DICER1

FH

KRAS

NF1

RAD50

SDHD

YAP1

BRAF

EGFR

FUBP1

LZTR1

NF2

RAD51

SETD2

YES1

BRCA1

EGLN1

GATA3

MAP2K1 (MEK1)

NRAS

RAD51B

SF3B1

BRCA2

EGLN2

GNA11

MAP2K2 (MEK2)

NTRK1

RAD51C

SMAD4

BRD4

EIF1AX

GNAQ

MAP2K4

NTRK2

RAD51D

SMARCA2

BRIP1

EPAS1

GNAS

MAP3K1

NTRK3

RAD52

SMARCA4

BUB1B

ERBB2

H3F3A

MAPK1

PALB2

RAD54L

SMARCB1

EMSY

ERBB3

HIST1H3B

MAX

PBRM1

RAF1

SMARCE1

CASP8

ERBB4

HIST1H3C

MC1R

PDCD1LG2

RASA1

SMO

 
 

Fusion Gene Panel

AKT3

ALK

BRAF

EGFR

ERBB4

ERG

FGFR1

FGFR2

FGFR3

MET

NOTCH1

NOTCH2

NRG1

NTRK1

NTRK2

NTRK3

NUTM1

PDGFRA

RAF1

RET

ROS1


Methodology:

The test is performed on DNA and RNA extracted from tumor-rich regions of formalin-fixed/paraffin-embedded tissue. The DNA and RNA (cDNA) NGS library preparations are both based on custom QiaSeq chemistry (Qiagen) that includes unique molecular indices for the assessment of library complexity. Sequencing is performed on Illumina NextSeq500/550 instruments and the data are analyzed through custom bioinformatics pipelines. The DNA library is generated by 9,229 custom-designed primer extension assays covering 613,343 base pairs across 225 cancer-related genes (whole exons of 199 genes, hotspot regions of 26 genes). This panel is routinely sequenced to an average read depth of ~2,000, providing high sensitivity for SNVs, in/dels and copy number alterations. Variants are identified using both FreeBayes and MuTect2 algorithms in a custom sequencing analysis pipeline. Included in the panel are 227 short repeats that are used to assess microsatellite instability. TMB is estimated by determining the number of likely somatic mutations and normalizing this to mutations per megabase of sequence.

The RNA panel consists of 309 custom-designed primer extension assays covering common breakpoints across 24 genes involved in clinically informative gene fusions. Using Starfusion software, the panel can identify any partner fused to these target genes. The panel can also detect oncogenic splice variants such as EGFRvIII and MET ex14del. Using a minimum output of 200,000 unique reads, this panel achieves a high level of sensitivity.

  • Input DNA: 20 ng
  • Minimum read depth per amplicon:  250

Specimen Requirements:

  • A paraffin block or
  • 10 unstained sections of tumor (4-5 microns)(15 sections for small biopsies)
  • Contact Client Services for shipping materials and procedures at (855) 535-1522.
A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information.

Test Performed (Days):

Twice weekly

Turn Around Time:

10-17 Calendar days

Shipment Sensitivity Requirements:

  • Keep specimen cool during transit, but do not ship on dry ice.
  • Please use the cold pack provided in the KDL shipping kit.
  • Ship the specimen overnight express, using the FedEx priority overnight label provided.
  • Contact Client Services for shipping materials and procedures at (855) 535-1522

References:

  1. Shaw AT, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27;370(13):1189-97.
  2. Shaw AT, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94.
  3. Shaw AT, et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Nov 20;371(21):1963-71.
  4. Elisei R, et al. Cabozantinib in progressive medullary thyroid cancer J Clin Oncol. 2013 Oct 10;31(29):3639-46.
  5. Dimitriadis E, et a. BRAF alterations in pediatric low grade gliomas and mixed neuronal-glial tumor. J Neurooncol. 2013 Jul;113(3):353-8.
  6. Graham RP, et al. Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma Hum Pathol. 2014 Aug;45(8):1630-8

Additional Info: