Topic Name

Message

If ARUP Consult does not answer your test selection and interpretation questions, or if you would like to suggest ways to improve content or usability, please send a message to the Consult editorial staff.

Please do not include any patient-specific or personal health information (PHI) in your message.

Email Address

An email address is not required, but providing one allows the ARUP Consult editorial staff to respond directly. ARUP will only use your email address to respond to your feedback. See the ARUP privacy policy for more information regarding email use.

CAPTCHA

What code is in the image?

Enter the characters shown in the image.

This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Solid Tumor Mutation Panel, Sequencing

3004294

Solid Tumor Mutation Panel, Sequencing 3004294

Method

Massively Parallel Sequencing

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	16^a
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	2^b
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, 18^b
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	5^b
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 11^b
MET	NM_001127500.2	2,^c 11, 13, 14, 15, 16, 19
MTOR	NM_004958.3	27-58
NOTCH1	NM_017617.4	26, 27, 34^d
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,^b14,^b 19, 21
PTEN	NM_000314.6	1,^b 2,^b 3, 4-9^b
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 variants^e
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 duplications^a	42	100	95.6-100.0
Medium insertions and duplications^b	10	100	82.9-100.0
Large insertions^c	1	100	22.9-100.0
Small deletions^a	80	100	97.6-100.0
Medium deletions^b	14	100	71.2-99.2
Large deletions^d	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

Sepulveda AR, Hamilton SR, Allegra CJ, et al. Molecular biomarkers for the evaluation of colorectal cancer: guideline from the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017;35(13):1453-1486.

31340094

Loriot Y, Necchi A, Park SH, et al. Erdafitinib in locally advanced or metastatic urothelial carcinoma. N Engl J Med. 2019;381(4):338-348.

28534687

Nikiforov YE. Role of molecular markers in thyroid nodule management: then and now [published correction appears in Endocr Pract. 2017;23(11):1362]. Endocr Pract. 2017;23(8):979-988.

Solid Tumor Mutation Panel, Sequencing

Disease Overview

Diagnosis

Prognosis and Treatment

Genetics

Genes

Variants Detected

Test Interpretation

Analytic Sensitivity

Results

Limitations

References

32228358

29220298

28622513

31124566

28165299

31340094

28534687

Feedback

Solid Tumor Mutation Panel, Sequencing

Disease Overview

Diagnosis

Prognosis and Treatment

Genetics

Genes

Variants Detected

Test Interpretation

Analytic Sensitivity

Results

Limitations

References

32228358

29220298

28622513

31124566

28165299

31340094

28534687