Solid Tumor Mutation Panel, Sequencing

Last Literature Review: August 2022 Last Update:
  • Use to assess for targeted variants that are useful for prognosis and/or treatment of individuals with solid tumor cancers, including melanoma, GIST, colorectal, bladder, and hepatocellular carcinomas, at initial diagnosis or in the presence of refractory disease
  • If the clinical indication is lung cancer, additional molecular genetic testing may be considered for detection of gene rearrangements and/or c-MET exon 14-skipping alterations.
  • For evaluation of microsatellite instability, additional molecular testing should be considered.

Individuals diagnosed with a solid tumor cancer may benefit from testing for genetic mutations and variants that can affect treatment options and prognosis. Solid tumor cancers that may benefit from this testing include melanoma,  gastrointestinal stromal tumors (GISTs),  hepatocellular carcinomas,  primary brain tumors,  colorectal,  bladder,  and thyroid cancer,  among others. Testing can be useful at initial diagnosis or in the presence of refractory disease.

Disease Overview

Diagnosis

  • Genetic targets contained in the panel, including extended RAS targets,  are relevant across the spectrum of solid tumors.
  • Identification of one or more variants may aid in diagnostic subclassification.

Prognosis and Treatment

  • Certain gene variants may have prognostic significance.
  • Certain gene variants may confer sensitivity or resistance to available targeted therapies.

Genetics

Genes

AKT1, ALK, APC, ATM, BRAF, CDH1, CDKN2A, CTNNB1, DDR2, EGFR, ERBB2, ERBB4, EZH2, FBXW7, FGFR1, FGFR2, FGFR3, GNA11, GNAQ, GNAS, HRAS, IDH1, IDH2, KDR, KIT, KRAS, MAP2K1, MET, MTOR, NOTCH1, NRAS, NTRK1, PDGFRA, PIK3CA, PTEN, RB1, RET, ROS1, SMAD4, SMO, STK11, TERT promoter, TP53, VHL

Variants Detected

  • This test is intended to detect somatic mutations, but germline alterations may also be detected.
  • The assay does not distinguish between somatic and germline findings.
  • Consultation with a genetic counselor is advised if there is any clinical suspicion for a germline alteration.
Solid Panel Targeted Regions
GeneAccession No.Targeted Exons
AKT1NM_001014431.13, 4, 6
ALKNM_004304.416-29
APCNM_000038.516a
ATMNM_000051.38, 9, 12, 17, 26, 34-36, 39, 50, 54-56, 59, 61, 63
BRAFNM_004333.411,b 14, 15
CDH1NM_004360.43, 8, 9
CDKN2ANM_000077.42b
CTNNB1NM_001904.33
DDR2NM_001014796.118
EGFRNM_005228.418-21
ERBB2NM_004448.38, 17-22
ERBB4NM_005235.23, 4, 6-9, 15, 23
EZH2NM_004456.416, 18b
FBXW7NM_033632.35, 8-11
FGFR1NM_023110.24, 7
FGFR2NM_000141.47, 9, 12
FGFR3NM_000142.47, 9, 14, 16, 18
GNA11NM_002067.45
GNAQNM_002072.45b
GNASNM_000516.58, 9
HRASNM_005343.32-4
IDH1NM_005896.34
IDH2NM_002168.34
KDRNM_002253.26, 7, 11, 19, 21, 26, 27, 30
KITNM_000222.22, 9, 10, 11, 13, 14, 15, 17, 18
KRASNM_004985.42, 3, 4
MAP2K1NM_002755.32,b 3, 6, 7,b 11b
METNM_001127500.22,c 11, 13, 14, 15, 16, 19
MTORNM_004958.327-58
NOTCH1NM_017617.426, 27, 34d
NRASNM_002524.42-5
NTRK1NM_002529.35-15, 17
PDGFRANM_006206.412, 14, 15, 18
PIK3CANM_006218.22, 5, 7, 8, 10,b 14,b 19, 21
PTENNM_000314.61,b 2,b 3, 4-9b
RB1NM_000321.24, 6, 10, 11, 14, 17, 18, 20, 21, 22
RETNM_020975.46, 7, 8, 10-13, 15, 16
ROS1NM_002944.27, 31-36, 38, 40, 41
SMAD4NM_005359.53-12
SMONM_005631.43, 5, 6, 9-11
STK11NM_000455.41, 4, 5, 6, 8
TERT PromoterNM_198253.2.1Selected promoter region variantse
TP53NM_000546.52-11
VHLNM_000551.31-3

ac.2390-c.2879, c.3128-c.3497, c.3730-4932

bExon known to contain known pseudogenes, homologous genomic regions, and/or low-mappability regions.

cc.374-c.743, c.815-c.1200+10

dc.7168-c.7657

eOnly c.-124C>T, c.-146C>T, c.-57 A>C, c.-125_124delinsTT, and c.-139_-138delinsTT hotspot promoter variants reported.

Test Interpretation

Analytic Sensitivity

Variant ClassNo. of Variants TestedPPA (%)PPA (%), 95% Tolerance at 95% Reliability
SNVs1779997.4-99.9
MNVs429382.2-98.0
Small insertions and duplicationsa4210095.6-100.0
Medium insertions and duplicationsb1010082.9-100.0
Large insertionsc110022.9-100.0
Small deletionsa8010097.6-100.0
Medium deletionsb1410071.2-99.2
Large deletionsd226442.9-81.1

a≤21 bp.

b22-60 bp.

c≥61 bp and ≤64 bp.

d≥61 bp and ≤13547 bp.

bp, base pairs; MNV, multinucleotide variant; PPA, positive percent agreement; SNV, single nucleotide variant

Results

ResultsVariants DetectedInterpretation
PositiveVariants in ≥1 of the 44 genes were detectedClinical relevance (diagnosis, prognosis, or therapy) will be correlated, if known
NegativeNo pathogenic variants were detectedn/a
n/a, not available

Limitations

  • Does not detect copy number alterations, translocations, microsatellite instability (MSI), gene rearrangements, and tumor mutational burden
  • Variants in areas outside the targeted genomic regions or below the limit of detection (LOD) of 5% variant allele frequency for SNVs or small- to medium-sized MNVs (<60 bp) will not be detected.
  • 10 ng input DNA from extracted tissue sample is minimally required, but 50 ng input DNA is recommended for optimal results.
  • Large variants (>60 bp) may not be detected.
  • Variants in known pseudogenes, homologous genomic regions, and/or low-mappability regions may not be detected (see the Solid Panel Targeted Regions table).
  • Not intended to detect minimal residual disease
  • Does not distinguish between somatic and germline variants

References

Related Information
Colorectal (Colon) Cancer
Gastrointestinal Stromal Tumors (GISTs)
Lynch Syndrome - Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
Non-Small Cell Lung Cancer Molecular Markers
Melanoma