Pancreas

BCL-10 is an N-terminal CARD (Caspase Recruitment Domain) containing protein that is involved in the adaptive immune response. It is also a substrate for MALT1. Mutations in the gene can lead to lymphoma, mucosa-associated lymphoid type. It is useful in the assessment of pancreatic tumors to distinguish acinar cell carcinoma from primitive neuroectodermal tumor (PNET), solid pseudopapillary tumor (SPT) and pancreatic blastoma (PB).

CancerTYPE ID is a proprietary molecular cancer classifier used to identify unknown or unclear tumor types and subtypes in patients with metastatic cancer. When ordered through NeoGenomics, classification with CancerTYPE ID is followed by tumor profiling for actionable biomarkers using the NeoTYPE^® Cancer Profile most appropriate for the tumor type identified by Cancer TYPE ID.^† Tech-only options for FISH and IHC within the NeoTYPE Cancer Profile are available.

CancerTYPE ID is performed and billed separately by NeoGenomics’ contracted reference laboratory, Biotheranostics, Inc., an independent CLIA-licensed and CAP-accredited reference laboratory. The test uses quantitative RT-PCR to measure the expression of 92 genes in the patient’s specimen and classifies the tumor by matching the gene expression profile to a database of more than 2000 known tumor types and subtypes. Using this technology, CancerTYPE ID can identify 50 different tumor types and subtypes, covering >95% of all solid tumors based on incidence.¹ The test reports a main cancer type with the highest probability, as well as a list of tumor types that may be ruled out with 95% confidence. 

^†CancerTYPE ID may be ordered as a stand-alone test directly from Biotheranostics, Inc. Please see www.cancertypeid.com.   

In situ hybridization for detection of cytomegalovirus (CMV) RNA.

Next-gen sequencing of all coding regions and intron-exon boundaries is performed concurrently for the following 73 genes: AKT1, APC, ATM, ATR, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CEBPA, CHEK1, CHEK2, CTNNA1, EPCAM, ETV6, FAM175A, GALNT12, GATA2, GEN1, GREM1, HOXB13, KLLN, MEN1, MLH1, MRE11A, MSH2, MSH6, MUTYH, MYH1, MYH2, MYH3, MYH4, MYH6, MYH7, MYH8, MYH9, MYH10, MYH11, MYH13, MYH14, MYH15, NBN, NTRK1, PALB2, PIK3CA, PMS2, POLD1, POLE, PPM1D, PRSS1, PTEN, RAD50, RAD51, RAD51C, RAD51D, RET, RUNX1, SDHB, SDHC, SDHD, SMAD4, STK11, TERC, TERT, TP53, TP53BP1, VHL, WT1, and XRCC2. Note: Patient and physician or genetic counselor signatures on the NeoGenomics Consent for Hereditary Cancer Genetic Testing form are required. Testing will be put on hold until signatures are received.

Bi-directional sequencing of exons 8 and 9 of the GNAS gene to detect mutation hot spots in codons R201 and Q227.

INSM1 is a transcription factor that is a sensitive and specific marker for neuroendocrine tumors.  It is a nuclear stain, and is as good if not better than synaptophysin and is superior to chromogranin. It is rarely expressed on adenocarcinoma or squamous cell carcinomas without neuroendocrine differentiation. 

Ki67 is a nuclear protein that is expressed in proliferating cells. Ki67 is preferentially expressed during late G1, S, M, and G2 phases of the cell cycle, while cells in the G0 (quiescent) phase are negative for this protein. Increased proliferative activity is associated with more aggressive tumor and decreased disease-free survival period.
Note: Computer-assisted image analysis for Ki-67 is only validated for breast cancer and neuroendocrine carcinoma.

Bi-directional sequencing of exon 4 of the KRAS gene corresponding to amino acids  R97 through Q150.  Codon 117 and 146 mutations are detected. For solid tumors, tumor enrichment is performed before extraction.  This test may be ordered separately or by reflex after standard KRAS Mutation Analysis. Testing is available separately or in combination with BRAF, HRAS and NRAS in the RAS/RAF Panel. Testing is approved for specimens from the state of New York.

Bi-directional sequencing of exons 2 and 3 of the KRAS gene. High-sensitivity sequencing is used for enhanced detection of mutations in codons 12, 13, 59, and 61.  For solid tumors, tumor enrichment is performed before extraction. Testing is available separately or in combination with BRAF, HRAS and NRAS in the RAS/RAF Panel. Testing is approved for specimens from the state of New York.  

The Lung NGS Fusion Profile is an RNA-based next-generation sequencing panel that detects translocations and fusions of the genes ALK, NTRK1, NTRK2, NTRK3, RET and ROS1 with known and novel fusion partners. Point mutations in select exons of these six genes are also detected. Examples of some of the published fusions detectable in this test include EML4-ALK, KIF5B-ALK, NPM1-ALK, CD74-NTRK1, MPRIP-NTRK1, TPM3-NTRK1, TRIM24-NTRK2, PAN3-NTRK2, ETV6-NTRK3, CCD6-RET (aka RET-PTC1), KIF5B-RET, NCOA4-RET (aka RET-PTC3), CD74-ROS1, SLC34A2-ROS1, and TPM3-ROS1.

This test may be used to select patients for therapy with the FDA-approved TRK inhibitor Vitrakvi^® (larotrectinib).

We recommend FISH as the primary method of ALK, RET, and ROS1 rearrangement detection. We suggest using this test for NTRK analysis and/or cases that fail to provide conclusive FISH results. See also NTRK NGS Fusion Profile and NTRK & RET NGS Fusion Profile.

Bi-directional Sanger sequencing of MET is performed using PCR primers designed to target hotspot mutations in exons 14, 16, 17 and 19.

PCR and fragment analysis of paired normal and tumor tissue to determine microsatellite instability (MSI) at the standard five NCI-recommended loci. Positive results are reported as MSI-high (at least two markers are unstable) or MSI-low (one marker is unstable).

A well-defined subtype of colorectal cancer (CRC) is characterized by deficiencies in the mismatch repair (MMR) pathway. MMR status may impact prognosis and benefit of adjuvant chemotherapy. MLH1, MSH2, MSH6, and PMS2 protein expression (as assessed by IHC) and microsatellite instability analysis (MSI) assessed by PCR are well-established tools to screen for Lynch syndrome (LS), and such testing is recommended for all new colorectal cancer diagnoses. MMR IHC and molecular MSI testing also serve as companion diagnostic tests in a wide range of solid tumors for selection of certain immuno-oncology therapies.

Mucin 1 (MUC1) is a high molecular weight glycoprotein that is found on the apical surface of many glandular epithelia, including the gastrointestinal, respiratory, urinary, reproductive tracts and some hematopoietic cell lineages. MUC1 has been implicated in progression of numerous types of cancer, including breast, colon, lung, gastric and pancreatic cancers. MUC1 expression in tumors is greatly increased and accompanied by altered aberrant expression patterns that become more diffuse when compared to the normal apically restricted pattern.

The NeoARRAY SNP/Cytogenetic Profile is available for hematological, solid tumor, and pregnancy loss indications. With the best genome-wide coverage available, this test employs an enhanced SNP microarray with over 2.6 million SNP and non-polymorphic markers for detection of copy number variants (deletions, duplications, and amplifications) and loss of heterozygosity or uniparental disomy (LOH or UPD) in any chromosome. Sensitivity and specificity for detection of copy number variants >400 kb is >99%. Testing may not reliably detect abnormalities present in less than 20% of the cells tested. Balanced rearrangements, including translocations and inversions, are not detectable by this method. Clients may request NeoARRAY on POC as the sole test, or they may order POC cytogenetics with reflex to NeoARRAY if the POC culture fails or if cytogenetic results are normal. For reflex orders, if there is no cell attachment or growth after 14 days in culture, a cytogenetics failure report will be issued and NeoARRAY will be performed. If there is limited cell attachment after 14 days in culture, NeoGenomics will contact the client for instructions. When array testing is not performed, a fee will be charged for DNA extraction (which is performed upon specimen receipt).

The NeoLAB™ Solid Tumor Monitor is a blood test that uses cell-free circulating tumor DNA (ctDNA) or RNA in combination with next-generation sequencing (NGS) to detect mutations in the following 48 genes: ABL1, AKT1, ALK, APC, ATM, BRAF, CDH1, CDKN2A, CSF1R, CTNNB1, EGFR, ERBB2, ERBB4, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO, SRC, STK11, TP53, and VHL. The EGFR T790 mutation is tested at high sensitivity (10^-4). Test orders include summary interpretation of all results together. NOTE: One-time baseline molecular testing at NeoGenomics on the solid tumor is required. Please see details in Specimen Requirements.

This profile analyzes 334 biomarkers through a combination of next-generation sequencing (NGS), other molecular methods, FISH, and IHC as listed below. Test orders include summary interpretation of all results to help guide treatment decisions. If Pan-TRK IHC is expressed or indeterminate, NTRK NGS Fusion Profile for NTRK1 fusions, NTRK2 fusions, and NTRK3 fusions will be added by reflex.

• FISH (9 FISH): ALK, BRAF,  HER2, MET, MYC, PDGFRA amplifications, PTEN, RET, ROS1 (tech-only available)
• IHC (2 biomarkers): PD-L1 22C3, Pan-TRK (tech-only available for PD-L1) PD-L1 IHC, Pan-TRK IHC
• NGS (322 genes + 1 biomarker): ABL1, ABL2, ACVR1B, AKT1, AKT2, AKT3, ALK, AMER1, APC, AR, ARAF, ARFRP1, ARID1A, ARID1B, ARID2, ASXL1, ATM, ATR, ATRX, AURKA, AURKB, AXIN1, AXL, BAP1, BARD1, BCL2, BCL2L1, BCL2L2, BCL6, BCOR, BCORL1, BLM, BRAF, BRCA1, BRCA2, BRD4, BRIP1, BTG1, BTK, C11orf30, CARD11, CBFB, CBL, CCND1, CCND2, CCND3, CCNE1, CD274, CD79A, CD79B, CDC73, CDH1, CDK12, CDK4, CDK6, CDK8, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CEBPA, CHD2, CHD4, CHEK1, CHEK2, CIC, CREBBP, CRKL, CRLF2, CSF1R, CTCF, CTNNA1, CTNNB1, CUL3, CXCR4, CYLD, DAXX, DDR2, DICER1, DNMT3A, DOT1L, EGFR, EP300, EPCAM, EPHA3, EPHA5, EPHA7, EPHB1, ERBB2, ERBB3, ERBB4, ERG, ERRFI1, ESR1, EZH2, FAM46C, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, FAS, FAT1, FBXW7, FGF10, FGF14, FGF19, FGF23, FGF3, FGF4, FGF6, FGFR1, FGFR2, FGFR3, FGFR4, FH, FLCN, FLT1, FLT3, FLT4, FOXL2, FOXP1, FRS2, FUBP1, GABRA6, GATA1, GATA2, GATA3, GATA4, GATA6, GID4, GLI1, GNA11, GNA13, GNAQ, GNAS, GPR124, GRIN2A, GRM3, GSK3B, H3F3A, HGF, HNF1A, HRAS, HSD3B1, HSP90AA1, IDH1, IDH2, IGF1R, IGF2, IKBKE, IKZF1, IL7R, INHBA, INPP4B, IRF2, IRF4, IRS2, JAK1, JAK2, JAK3, JUN, KAT6A, KDM5A, KDM5C, KDM6A, KDR, KEAP1, KEL, KIT, KLHL6, KMT2A, KMT2C, KMT2D, KRAS, LMO1, LRP1B, LYN, LZTR1, MAGI2, MAP2K1, MAP2K2, MAP2K4, MAP3K1, MCL1, MDM2, MDM4, MED12, MEF2B, MEN1, MET, MITF, MLH1, MPL, MRE11A, MSH2, MSH6, MTOR, MUTYH, MYC, MYCL, MYCN, MYD88, NBN, NF1, NF2, NFE2L2, NFKBIA, NKX2-1, NOTCH1, NOTCH2, NOTCH3, NPM1, NRAS, NSD1, NTRK1, NTRK2, NTRK3, NUP93, PAK3, PALB2, PARK2, PAX5, PBRM1, PDCD1LG2, PDGFRA, PDGFRB, PDK1, PIK3C2B, PIK3CA, PIK3CB, PIK3CG, PIK3R1, PIK3R2, PLCG2, PMS2, POLD1, POLE, PPP2R1A, PRDM1, PREX2, PRKAR1A, PRKCI, PRKDC, PRSS8, PTCH1, PTEN, PTPN11, QKI, RAC1, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD54L, RAF1, RANBP2, RARA, RB1, RBM10, RET, RICTOR, RNF43, ROS1, RPTOR, RUNX1, RUNX1T1, SDHA, SDHB, SDHC, SDHD, SETD2, SF3B1, SLIT2, SMAD2, SMAD3, SMAD4, SMARCA4, SMARCB1, SMO, SNCAIP, SOCS1, SOX10, SOX2, SOX9, SPEN, SPOP, SPTA1, SRC, STAG2, STAT3, STAT4, STK11, SUFU, SYK, TAF1, TBX3, TERC, TERT, TET2, TGFBR2, TNFAIP3, TNFRSF14, TOP1, TOP2A, TP53, TSC1, TSC2, TSHR, U2AF1, VEGFA, VHL, WISP3, WT1, XPO1, ZBTB2, ZNF217, ZNF703, Tumor Mutation Burden (TMB)

This profile analyzes 29 biomarkers through a combination of next-generation sequencing (NGS), FISH, and IHC as listed below. Test orders include summary interpretation of all results to help guide treatment decisions. If Pan-TRK IHC is expressed or indeterminate, NTRK NGS Fusion Profile for NTRK1 fusions, NTRK2 fusions, and NTRK3 fusions will be added by reflex.

• NGS (24 genes + 1 biomarker): AKT1, BRAF, EGFR, FGFR1, FGFR2, FGFR3, GNAS, HRAS, IDH1, IDH2, JAK3, KIT, KRAS, MET, NOTCH1, NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, SMAD4, SMO, SRC, TP53  and Tumor Mutation Burden (TMB)
• FISH (2 FISH): MET, PTEN (tech-only available)
• IHC (2 biomarker): PD-L1, Pan-TRK (tech-only available for PD-L1)

The NeoTYPE Pancreas Tumor Profile analyzes 29 biomarkers through a combination of next-generation sequencing (NGS), other molecular methods, FISH, and IHC as listed below. Test orders include summary interpretation of all results to help guide treatment decisions. BRCA1/2 testing will be performed unless opted out. If Pan-TRK IHC is expressed or indeterminate, NTRK NGS Fusion Profile for NTRK1 fusions, NTRK2 fusions, and NTRK3 fusions will be added by reflex.

• NGS (22 genes + 1 biomarker): ARID1A, BRAF, BRCA1, BRCA2, CDKN2A, EGFR, ERBB2, ERBB4, FGFR1, FGFR2, FGFR3, HRAS, KIT, KRAS, MET, NOTCH1, NRAS, PALB2, PIK3CA, PTEN, SMO, TP53 and Tumor Mutation Burden (TMB)
• Other Molecular (1 biomarker): Microsatellite Instability (MSI) 
• FISH (3 FISH): HER2, MET, PTEN (tech-only available)
• IHC (2 biomarkers): PD-L1 22C3, Pan-TRK (tech-only available for PD-L1)
   

This Profile analyzes 51 biomarkers through a combination of next-generation sequencing (NGS) and IHC as listed below. Test orders include summary interpretation of all results to help guide treatment decisions. If Pan-TRK IHC is expressed or indeterminate, NTRK NGS Fusion Profile for NTRK1 fusions, NTRK2 fusions, and NTRK3 fusions will be added by reflex.

• NGS (48 genes + 1 biomarker): ABL1, AKT1, ALK, APC, ATM, BRAF, CDH1, CDKN2A, CSF1R, CTNNB1, EGFR, ERBB2, ERBB4, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, NRAS, PDGFRA,  PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO, SRC, STK11, TP53, VHL and Tumor Mutation Burden (TMB)
• IHC (2 biomarkers): PD-L1 22C3, Pan-TRK (tech-only available for PD-L1)
   

The NTRK & RET NGS Fusion Profile is an RNA-based next-generation sequencing panel that detects translocations and fusions of the genes NTRK1, NTRK2, NTRK3 and RET with known and novel fusion partners. Point mutations in select exons of these four genes are also detected. Examples of some of the published fusions detectable in this test include CD74-NTRK1, LMNA-NTRK1, MPRIP-NTRK1, TPM3-NTRK1, SQSTM1-NTRK1, PPL-NTRK1, AFAP1-NTRK2, PAN3-NTRK2, TRIM24-NTRK2, BTBD1-NTRK3, ETV6-NTRK3, CCD6-RET (aka RET-PTC1), KIF5B-RET, and NCOA4-RET (aka RET-PTC3).

This test may be used to select patients for therapy with the FDA-approved TRK inhibitor Vitrakvi^® (larotrectinib).

See also NTRK NGS Fusion Profile and Lung NGS Fusion Profile.

The NTRK NGS Fusion Profile is an RNA-based next-generation sequencing panel that detects translocations and fusions of the Neurotrophic Tropomyosin-Related Kinase (NTRK) genes NTRK1, NTRK2, and NTRK3 with known and novel fusion partners. Point mutations in select exons of these three genes are also detected. Examples of some of the published fusions detectable in this test include CD74-NTRK1, LMNA-NTRK1, MPRIP-NTRK1, TPM3-NTRK1, SQSTM1-NTRK1, PPL-NTRK1, AFAP1-NTRK2, PAN3-NTRK2, TRIM24-NTRK2, BTBD1-NTRK3, and ETV6-NTRK3.

This test may be used to select patients for therapy with the FDA-approved TRK inhibitor Vitrakvi^® (larotrectinib).

See also Lung NGS Fusion Profile and NTRK & RET NGS Fusion Profile.

RRM1 is crucial for DNA synthesis and damage repair. High levels of RRM1 are associated with G2 cell cycle arrest and increased apoptosis in vitro.

Bi-directional sequencing of TP53 exons 4-9.