Solid Tumor Mutation Panel, Sequencing

Content Review: August 2022 Last Update: August 2023
  • 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
Gene Accession No. Targeted Exons

AKT1

NM_001014431.1

3, 4, 6

ALK

NM_004304.4

16-29

APC

NM_000038.5

16a

ATM

NM_000051.3

8, 9, 12, 17, 26, 34-36, 39, 50, 54-56, 59, 61, 63

BRAF

NM_004333.4

11,b 14, 15

CDH1

NM_004360.4

3, 8, 9

CDKN2A

NM_000077.4

2b

CTNNB1

NM_001904.3

3

DDR2

NM_001014796.1

18

EGFR

NM_005228.4

18-21

ERBB2

NM_004448.3

8, 17-22

ERBB4

NM_005235.2

3, 4, 6-9, 15, 23

EZH2

NM_004456.4

16, 18b

FBXW7

NM_033632.3

5, 8-11

FGFR1

NM_023110.2

4, 7

FGFR2

NM_000141.4

7, 9, 12

FGFR3

NM_000142.4

7, 9, 14, 16, 18

GNA11

NM_002067.4

5

GNAQ

NM_002072.4

5b

GNAS

NM_000516.5

8, 9

HRAS

NM_005343.3

2-4

IDH1

NM_005896.3

4

IDH2

NM_002168.3

4

KDR

NM_002253.2

6, 7, 11, 19, 21, 26, 27, 30

KIT

NM_000222.2

2, 9, 10, 11, 13, 14, 15, 17, 18

KRAS

NM_004985.4

2, 3, 4

MAP2K1

NM_002755.3

2,b 3, 6, 7,b 11b

MET

NM_001127500.2

2,c 11, 13, 14, 15, 16, 19

MTOR

NM_004958.3

27-58

NOTCH1

NM_017617.4

26, 27, 34d

NRAS

NM_002524.4

2-5

NTRK1

NM_002529.3

5-15, 17

PDGFRA

NM_006206.4

12, 14, 15, 18

PIK3CA

NM_006218.2

2, 5, 7, 8, 10,b 14,b 19, 21

PTEN

NM_000314.6

1,b 2,b 3, 4-9b

RB1

NM_000321.2

4, 6, 10, 11, 14, 17, 18, 20, 21, 22

RET

NM_020975.4

6, 7, 8, 10-13, 15, 16

ROS1

NM_002944.2

7, 31-36, 38, 40, 41

SMAD4

NM_005359.5

3-12

SMO

NM_005631.4

3, 5, 6, 9-11

STK11

NM_000455.4

1, 4, 5, 6, 8

TERT Promoter

NM_198253.2.1

Selected promoter region variantse

TP53

NM_000546.5

2-11

VHL

NM_000551.3

1-3

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 Class No. of Variants Tested PPA (%) PPA (%), 95% Tolerance at 95% Reliability

SNVs

177

99

97.4-99.9

MNVs

42

93

82.2-98.0

Small insertions and duplicationsa

42

100

95.6-100.0

Medium insertions and duplicationsb

10

100

82.9-100.0

Large insertionsc

1

100

22.9-100.0

Small deletionsa

80

100

97.6-100.0

Medium deletionsb

14

100

71.2-99.2

Large deletionsd

22

64

42.9-81.1

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

Results Variants Detected Interpretation

Positive

Variants in ≥1 of the 44 genes were detected

Clinical relevance (diagnosis, prognosis, or therapy) will be correlated, if known

Negative

No pathogenic variants were detected

n/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