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Cancer Sequencing and Deletion/Duplication Panel

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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TEST METHODS

Sequencing and Deletion/Duplication Testing via aCGH

Test Code TestCPT Code Copy CPT Codes
1355 APC 81201, 81203 Add to Order
ATM 81408, 81479
BAP1 81479, 81479
BLM 81479, 81479
BMPR1A 81479, 81479
BRCA1 81214, 81479
BRCA2 81216, 81479
BRIP1 81479, 81479
BUB1B 81479, 81479
CDH1 81406, 81479
CDK4 81479, 81479
CDKN2A 81404, 81479
CHEK2 81479, 81479
DICER1 81479, 81479
EPCAM 81479, 81403
KIT 81479, 81479
MEN1 81405, 81403
MET 81479, 81479
MLH1 81292, 81294
MSH2 81295, 81297
MSH6 81298, 81300
MUTYH 81406, 81479
NBN 81479, 81479
NF1 81408, 81479
PALB2 81406, 81479
PMS2 81317, 81319
PPM1D 81479, 81479
PTEN 81321, 81323
RAD51C 81479, 81479
RAD51D 81479, 81479
SMAD4 81406, 81405
STK11 81405, 81404
TP53 81405, 81479
VHL 81404, 81403
WT1 81405, 81479
Full Panel Price* $1390.00
Test Code Test Total Price CPT Codes Copy CPT Codes
1355 Genes x (35) $1390.00 81201, 81203, 81214, 81216, 81292, 81294, 81295, 81297, 81298, 81300, 81317, 81319, 81321, 81323, 81403(x3), 81404(x3), 81405(x5), 81406(x4), 81408(x2), 81479(x39) Add to Order
Pricing Comment

NF1 and STK11 are analyzed by Multiplex Ligation-dependent Probe Amplification. If you would like to order a subset of these genes contact us to discuss pricing.

Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity

Genes tested in this panel have been implicated in hereditary cancer and although individually these genes may be involved in a minority of cancers, the combination of highly, moderately and mildly penetrant pathogenic variants may be responsible for a significant portion of these hereditary cancers. See "Related Tests" section for a full description of each individual disorder.

Clinical sensitivity of the tested genes is given based on each syndrome. Deletion and duplication analysis is not available for BAP1, BUB1B, and MET genes. For CHEK2, only exons 8-10 will be analyzed, which includes all known deletions. Gross deletions/duplications have been reported in up to 12% of APC mutation positive patient samples (Jasperson and Burt 2011). Approximately 1-2% of Ataxia Telangiectasia patients have large genomic deletions involving the ATM gene that can be detected using aCGH (Gatti 2010). Gross deletions of multiple exons in the BLM gene account for approximately 5% of Bloom Syndrome (German et al. 2007). This test is predicted to identify a BMPR1A mutation in 1-2% and a SMAD4 mutation in 2-9% of patients diagnosed with JPS (Haidle and Howe 2011). Pathogenic variants will be detected by copy number analysis in 10% of HBOC individuals with an identifiable germline mutation. Previously, BRCA1 variants were observed in 90% of these cases and BRCA2 variants in 10% of these cases (Petrucelli 2013). Large rearrangements (e.g. deletions, duplications, tripications), including the five most commonly reported BRCA1 alterations (Hendrickson et al. 2005), can be detected using this test. High-risk patients, defined as individuals with early onset ( Large deletions that usually cannot be detected via sequencing have been detected in the CDH1 gene in up to 4% of patients (Kaurah and Huntsman 2011). Clinical sensitivity is not known for KIT mutations in GIST; however gross deletions have been reported for Piebaldism (Ezoe et al. 1995). Gross deletions of the MEN1 gene have been detected in up to 4% of patients (Giusti et al. 2012). Lynch syndrome is attributed to deletions in the MLH1, MSH2, MSH6, and PMS2 genes in approximately 5%, 20%, 7% and 20% of cases, respectively (Kohlmann and Gruber 2012). EPCAM deletions account for 1-3% of Lynch syndrome cases (Kohlmann and Gruber 2012). Deletions in the NF1 gene have been detected in 5% of individuals with Neurofibromatosis Type 1 (Friedman 2012). This test is predicted to detect causative PTEN mutations in ~11% of patients with BRRS but not known for other PTEN related disorders (Eng 2003). Approximately 45% of patients with a positive family history or 21% of patients with no family history of Peutz-Jeghers syndrome will have a pathogenic variant in STK11 by deletion analysis (McGarrity et al. 2013). Deletions in the TP53 gene have been detected in 1% of Li-Fraumeni cases (Schneider et al. 2013). Up to 28% of VHL causative mutations involve gross deletions (Frantzen et al. 1993). The clinical sensitivity of large deletions and duplications for the BRIP1, CDK4, CDKN2A, DICER1, MUTYH, NBN, PALB2, PPM1D, RAD51C, RAD51D and WT1 genes is not known but large duplications/deletions have been reported for most of these genes (Human Mutation Database).

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Clinical Features

Hereditary cancer syndromes have been observed in approximately 5-10% of diagnosed cancers (Mauer et al. 2013). Hereditary cancers tend to occur at an earlier age (i.e. < 50 years), tumors often occur bilaterally and/or are multifocal, consist of multiple affected family members, may include a less frequent affected gender (i.e. breast cancer in males), can be associated with other clinical features, and occur with a higher predisposition in specific ethnicities, such as the Ashkenazi Jewish population (Lindor et al. 2008). The results of analyzing a group of hereditary cancers can be important for counseling and treatment (O’Daniel and Lee 2012; Imyanitov and Byrski 2013). Additionally, assessment of multiple genes associated with hereditary cancers can be useful in determining personal or familial risks (Foulkes 2008).

Genetics

This NextGen test analyzes multiple genes involved in multiple hereditary cancer syndromes which are inherited in an autosomal dominant manner. Several types of cancers may be found in a pedigree and this test may help in the differential diagnosis and rule out particular syndromes by simultaneously analyzing multiple genes involved in hereditary cancers.

Breast & Ovarian Cancer - ATM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MEN1, NBN, PALB2, PPM1D, PTEN, RAD51C, RAD51D, STK11, TP53

DICER1 Syndrome - DICER1

Gastrointestinal Cancers - APC, ATM, BLM, BMPR1A, BUB1B, CDH1, CHEK2, EPCAM, KIT, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, TP53

Li-Fraumeni Syndrome - TP53

Melanoma Predisposition - BAP1, CDK4, CDKN2A

Pancreatic Cancer - APC, ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, TP53

Renal Cancer - MET, VHL, WT1

Pathogenic variants in the exon 1B promoter of APC have also been associated with gastric adenocarcinoma and proximal polyposis of the stomach (Li et al. 2016).

See individual gene test descriptions for information on clinical features and molecular biology of gene products.

Testing Strategy

The Cancer NextGen Sequencing Panel analyzes 35 genes that have been associated with hereditary cancers. For this NGS panel, the full coding regions, plus ~20bp of non-coding DNA flanking each exon, are sequenced for each of the genes listed below. Sequencing is accomplished by capturing specific regions with an optimized solution-based hybridization method, followed by massively parallel sequencing of the captured DNA fragments. Additional Sanger sequencing is performed for any regions not captured or with insufficient number of sequence reads, including the exon 1B promoter region of APC. All pathogenic, undocumented and questionable variant calls are confirmed by Sanger sequencing.

Due to known PMS2 pseudogenes, the PMS2 gene is also analyzed via Sanger sequencing using a long-range PCR strategy.

Please note that for deletion/duplication testing, NF1 and STK11 are analyzed by Multiplex Ligation-dependent Probe Amplification.

Each gene/group of genes can also be tested using our Sanger sequencing and Deletion/Duplication assays. Please see our test menu.

Indications for Test

Individuals with a clinical presentation of a cancer syndrome or a family history of cancer. Clinical presentation or family history includes early-onset cancer (i.e. multiple primary cancers, multiple family members with cancer, and individuals with an Ashkenazi descent with a concern for cancer. Earlier detection of clinical abnormalities may lead to earlier treatment and better outcomes.

This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

Diseases

Name Inheritance OMIM ID
Adenomatous Polyposis Coli 175100
Bannayan-Riley-Ruvalcaba Syndrome 153480
Bloom Syndrome 210900
Breast-Ovarian Cancer, Familial 1 604370
Breast-Ovarian Cancer, Familial 2 612555
Breast-Ovarian Cancer, Familial 4 614291
Cowden Disease 158350
Cutaneous Malignant Melanoma 1 155600
Familial Cancer Of Breast 114480
Fanconi Anemia, Complementation Group J 609054
Fanconi Anemia, Complementation Group N 610832
Fanconi Anemia, Complementation Group O 613390
Gastrointestinal Stromal Tumors 606764
Goiter, Multinodular 1, With Or Without Sertoli-Leydig Cell Tumors 138800
Hereditary Diffuse Gastric Cancer 137215
Hereditary Mixed Polyposis Syndrome 2 610069
Hereditary Nonpolyposis Colorectal Cancer Type 4 614337
Hereditary Nonpolyposis Colorectal Cancer Type 5 614350
Hereditary Nonpolyposis Colorectal Cancer Type 8 613244
Juvenile Polyposis Syndrome 174900
Juvenile Polyposis/Hereditary Hemorrhagic Telangiectasia Syndrome 175050
Li-Fraumeni Syndrome 151623
Lynch Syndrome I 120435
Lynch Syndrome II 609310
Malignant Mesothelioma 156240
Melanoma Astrocytoma Syndrome 155755
Melanoma, Cutaneous Malignant 2 155601
Melanoma, Cutaneous Malignant 3 609048
Melanoma-Pancreatic Cancer Syndrome 606719
Mosaic Variegated Aneuploidy Syndrome 257300
Multiple Endocrine Neoplasia, Type 1 131100
Myh-Associated Polyposis 608456
Neurofibromatosis, Type 1 162200
Pancreatic Cancer 2 613347
Pancreatic Cancer 3 613348
Pancreatic Cancer 4 614320
Peutz-Jeghers Syndrome 175200
Pleuropulmonary Blastoma 601200
Premature Chromatid Separation Trait 176430
Prostate Cancer 176807
Renal Cell Carcinoma, Papillary, 1 605074
Tumor Predisposition Syndrome 614327
Von Hippel-Lindau Syndrome 193300
Wilms' Tumor 194070

Related Tests

Name
Ataxia telangiectasia Syndrome via the ATM Gene
Autism Spectrum Disorders and Intellectual Disability (ASD-ID) Comprehensive Panel
Bloom's Syndrome via the BLM Gene
Chromosomal Instability Syndromes Sequencing Panel
Colorectal Cancer Sequencing And Deletion/Duplication Panel
DICER1 Syndrome via the DICER1 Gene
Disorders of Sex Development and Infertility Sequencing Panel
Disorders of Sex Development Sequencing Panel
Familial Adenomatous Polyposis via the APC Gene
Familial Gastrointestinal Stromal Tumors (GISTs) via the PDGFRA Gene
Fanconi Anemia Sequencing Panel
Fanconi Anemia via the BRCA2/FANCD1 Gene
Fanconi Anemia via the BRIP1/FANCJ Gene
Fanconi Anemia via the PALB2/FANCN Gene
Fanconi Anemia via the RAD51C/FANCO Gene
Female Infertility Sequencing Panel
Hereditary Breast and Ovarian Cancer BRCA1/2 Sequencing and Deletion/Duplication Panel
Hereditary Breast and Ovarian Cancer Syndrome - HBOC EXPANDED Sequencing and Deletion/Duplication Panel
Hereditary Breast and Ovarian Cancer Syndrome - HBOC HIGH RISK Sequencing and Deletion/Duplication Panel
Hereditary Breast and Ovarian Cancer via the BARD1 Gene
Hereditary Breast and Ovarian Cancer via the RAD50 Gene
Hereditary Breast and Ovarian Cancer via the RAD51D Gene
Hereditary Breast Cancer via the CHEK2 Gene
Hereditary Diffuse Gastric Cancer via the CDH1 Gene
Hereditary Hemorrhagic Telangiectasia (HHT) Sequencing Panel
Hereditary Myelodysplastic Syndrome (MDS) / Acute Myeloid Leukemia (AML) Sequencing Panel
Hereditary Papillary Renal Cell Carcinoma via the MET Gene
Hereditary Paraganglioma-Pheochromocytoma Syndrome Sequencing Panel
Juvenile Polyposis Syndrome (JPS) and Hereditary Hemorrhagic Telangiectasia (HHT) via the SMAD4 Gene
Juvenile Polyposis Syndrome (JPS) via the BMPR1A Gene
Li-Fraumeni Syndrome via the TP53 Gene
Lynch Syndrome Sequencing and Deletion/Duplication Panel
Lynch Syndrome via the EPCAM Gene
Lynch Syndrome via the MLH1 Gene
Lynch Syndrome via the MSH2 Gene
Lynch Syndrome via the PMS2 Gene
Lynch Syndrome via the MSH6 Gene
Male Infertility Sequencing Panel
Melanoma Predisposition via the CDK4 Gene
Melanoma Predisposition via the CDKN2A Gene
Mosaic Variegated Aneuploidy Syndrome via the BUB1B Gene
Multiple Endocrine Neoplasia Type 1 via the MEN1 Gene
MUTYH Associated Polyposis (MAP) Syndrome via the MUTYH Gene
Nephrotic Syndrome (NS)/Focal Segmental Glomerulosclerosis (FSGS) Sequencing Panel
Neurofibromatosis Type 1 and Legius Syndrome Sequencing Panel
Neurofibromatosis Type 1 and Related Disorders via the NF1 Gene
Neurofibromatosis Type 1 and Related Disorders via the NF1 Gene
Nijmegen Breakage Syndrome via the NBN Gene
Pancreatic Cancer Sequencing Panel
Peutz-Jeghers Syndrome via the STK11 Gene
Peutz-Jeghers Syndrome via the STK11 Gene
Piebaldism and Familial Gastrointestinal Stromal Tumors (GISTs) via the KIT Gene
PTEN Hamartoma Tumor Syndrome via the PTEN Gene
Renal Cancer Sequencing Panel
Steroid-Resistant Nephrotic syndrome via the WT1 Gene
Tumor Predisposition Syndrome, Uveal Melanoma and Mesothelioma via the BAP1 Gene
Von Hippel-Lindau Disease via the VHL Gene
Wilms Tumor via the WT1 Gene

CONTACTS

Genetic Counselors
Geneticist
Citations
  • Eng C. 2003. PTEN: One Gene, Many Syndromes. Human Mutation 22: 183–198. PubMed ID: 12938083
  • Ezoe K, Holmes SA, Ho L, Bennett CP, Bolognia JL, Brueton L, Burn J, Falabella R, Gatto EM, Ishii N. 1995. Novel mutations and deletions of the KIT (steel factor receptor) gene in human piebaldism. American journal of human genetics 56: 58-66. PubMed ID: 7529964
  • Foulkes WD. 2008. Inherited susceptibility to common cancers. New England Journal of Medicine 359: 2143–2153. PubMed ID: 19005198
  • Frantzen C, Links TP, Giles RH. 1993. Von Hippel-Lindau Disease. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle,. PubMed ID: 20301636
  • Friedman J. 2012. Neurofibromatosis 1. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301288
  • Gatti R. 2010. Ataxia-Telangiectasia. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301790
  • German J, Sanz MM, Ciocci S, Ye TZ, Ellis NA. 2007. Syndrome-causing mutations of the BLM gene in persons in the Bloom’s Syndrome Registry. Human Mutation 28: 743–753. PubMed ID: 17407155
  • Giusti F, Marini F, Brandi ML. 2012. Multiple Endocrine Neoplasia Type 1. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301710
  • Human Gene Mutation Database (Bio-base).
  • Imyanitov EN, Byrski T. 2013. Systemic treatment for hereditary cancers: a 2012 update. Hereditary Cancer in Clinical Practice 11: 2. PubMed ID: 23548133
  • Jasperson KW, Burt RW. 2011. APC-Associated Polyposis Conditions. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301519
  • Judkins T, Rosenthal E, Arnell C, Burbidge LA, Geary W, Barrus T, Schoenberger J, Trost J, Wenstrup RJ, Roa BB. 2012. Clinical significance of large rearrangements in BRCA1 and BRCA2. Cancer 118: 5210–5216. PubMed ID: 22544547
  • Kaurah P, Huntsman DG. 2011. Hereditary Diffuse Gastric Cancer. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301318
  • Kohlmann W, Gruber SB. 2012. Lynch Syndrome. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301390
  • Larsen Haidle J, Howe JR. 2011. Juvenile Polyposis Syndrome. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301642
  • Li J. et al. 2016. American Journal of Human Genetics. 98: 830-42. PubMed ID: 27087319
  • Lindor NM, McMaster ML, Lindor CJ, Greene MH. 2008. Concise Handbook of Familial Cancer Susceptibility Syndromes - Second Edition. JNCI Monographs 2008: 3–93. PubMed ID: 18559331
  • Mauer CB, Pirzadeh-Miller SM, Robinson LD, Euhus DM. 2013. The integration of next-generation sequencing panels in the clinical cancer genetics practice: an institutional experience. Genetics in Medicine. PubMed ID: 24113346
  • McGarrity TJ, Amos CI, Frazier ML, Wei C. 2013. Peutz-Jeghers Syndrome. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301443
  • O’Daniel JM, Lee K. 2012. Whole-genome and whole-exome sequencing in hereditary cancer: impact on genetic testing and counseling. The Cancer Journal 18: 287–292. PubMed ID: 22846728
  • Schneider K, Zelley K, Nichols KE, Garber J. 2013. Li-Fraumeni Syndrome. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301488
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TEST METHODS

NextGen Sequencing and Deletion/Duplication Testing Via Array Comparative Genomic Hybridization

Test Procedure

NextGen Sequencing

We use a combination of Next Generation Sequencing (NGS) and Sanger sequencing technologies to cover the full coding regions of the listed genes plus ~20 bases of non-coding DNA flanking each exon.  As required, genomic DNA is extracted from the patient specimen.  For NGS, patient DNA corresponding to these regions is captured using an optimized set of DNA hybridization probes.  Captured DNA is sequenced using Illumina’s Reversible Dye Terminator (RDT) platform (Illumina, San Diego, CA, USA).  Regions with insufficient coverage by NGS are covered by Sanger sequencing.  All pathogenic, likely pathogenic, or variants of uncertain significance are confirmed by Sanger sequencing.

For Sanger sequencing, Polymerase Chain Reaction (PCR) is used to amplify targeted regions.  After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.

Patient DNA sequence is aligned to the genomic reference sequence for the indicated gene region(s). All differences from the reference sequences (sequence variants) are assigned to one of five interpretation categories, listed below, per ACMG Guidelines (Richards et al. 2015).

(1) Pathogenic Variants
(2) Likely Pathogenic Variants
(3) Variants of Uncertain Significance
(4) Likely Benign Variants
(5) Benign, Common Variants

Human Genome Variation Society (HGVS) recommendations are used to describe sequence variants (http://www.hgvs.org).  Rare variants and undocumented variants are nearly always classified as likely benign if there is no indication that they alter protein sequence or disrupt splicing.

Deletion/Duplication Testing via aCGH

As required, DNA is extracted from the patient specimen. Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product.  The combined sample is loaded onto the designed array and hybridized for at least 22 hours at 65ºC.  Arrays are then washed and scanned immediately with 2.5 µM resolution.  Only data for the gene(s) of interest for each patient are extracted and analyzed.

PreventionGenetics’ high density gene-centric (HDGC) aCGH is designed to have comprehensive coverage for both coding and non-coding regions for each targeted gene with very high density probe coverage.  The average probe spacing within each exon is 47 bp or a minimum of three probes per exon covering all targeted exons and UTRs.  The average probe spacing is 289 bp covering all intronic, 2kb upstream and downstream regions of each targeted gene.  In addition, the flanking 300-bp intronic sequence on either side of targeted exons has enriched probe coverage.  Therefore, PreventionGenetics’ aCGH enables the detection of relatively small deletion and amplification mutations within a single exon of a given gene or deletion and amplification mutations encompassing the entire gene.

Analytical Validity

NextGen Sequencing

As of March 2016, 6.36 Mb of sequence (83 genes, 1557 exons) generated in our lab was compared between Sanger and NextGen methodologies. We detected no differences between the two methods. The comparison involved 6400 total sequence variants (differences from the reference sequences). Of these, 6144 were nucleotide substitutions and 256 were insertions or deletions. About 65% of the variants were heterozygous and 35% homozygous. The insertions and deletions ranged in length from 1 to over 100 nucleotides.

In silico validation of insertions and deletions in 20 replicates of 5 genes was also performed. The validation included insertions and deletions of lengths between 1 and 100 nucleotides. Insertions tested in silico: 2200 between 1 and 5 nucleotides, 625 between 6 and 10 nucleotides, 29 between 11 and 20 nucleotides, 25 between 21 and 49 nucleotides, and 23 at or greater than 50 nucleotides, with the largest at 98 nucleotides. All insertions were detected. Deletions tested in silico: 1813 between 1 and 5 nucleotides, 97 between 6 and 10 nucleotides, 32 between 11 and 20 nucleotides, 20 between 21 and 49 nucleotides, and 39 at or greater than 50 nucleotides, with the largest at 96 nucleotides. All deletions less than 50 nucleotides in length were detected, 13 greater than 50 nucleotides in length were missed. Our standard NextGen sequence variant calling algorithms are generally not capable of detecting insertions (duplications) or heterozygous deletions greater than 100 nucleotides. Large homozygous deletions appear to be detectable. 

Deletion/Duplication Testing via aCGH

PreventionGenetics’ high density gene-centric custom designed aCGH enables the detection of relatively small deletion and amplification mutations (down to ~300 bp) within a single exon of a given gene or deletion and amplification mutations encompassing the entire gene. PreventionGenetics has established and verified this test’s accuracy and precision.

Analytical Limitations

NextGen Sequencing

Interpretation of the test results is limited by the information that is currently available.  Better interpretation should be possible in the future as more data and knowledge about human genetics and this specific disorder are accumulated.

When Sanger sequencing does not reveal any difference from the reference sequence, or when a sequence variant is homozygous, we cannot be certain that we were able to detect both patient alleles.  Occasionally, a patient may carry an allele which does not amplify, due to a large deletion or insertion.   In these cases, the report will contain no information about the second allele.  Our Sanger and NGS Sequencing tests are generally not capable of detecting Copy Number Variants (CNVs).

We sequence all coding exons for each given transcript, plus ~20 bp of flanking non-coding DNA for each exon.  Test reports contain no information about other portions of the gene, such as regulatory domains, deep intronic regions or any currently uncharacterized alternative exons.

In most cases, we are unable to determine the phase of sequence variants.  In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants due to somatic mosaicism is limited.  Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR.

Unless otherwise indicated, DNA sequence data is obtained from a specific cell-type (usually leukocytes from whole blood).   Test reports contain no information about the DNA sequence in other cell-types.

We cannot be certain that the reference sequences are correct.

Rare, low probability interpretations of sequencing results, such as for example the occurrence of de novo mutations in recessive disorders, are generally not included in the reports.

We have confidence in our ability to track a specimen once it has been received by PreventionGenetics.  However, we take no responsibility for any specimen labeling errors that occur before the sample arrives at PreventionGenetics.

Deletion/Duplication Testing via aCGH

Any copy number changes smaller than 300bps (within the targeted region) may not be detected by our array.

This array may not detect deletion and amplification mutations present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype

Breakpoints, if happened outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory

Order Kits

Ordering Options


myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
REQUISITION FORM
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

SPECIMEN TYPES
WHOLE BLOOD

(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.

DNA

(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.

CELL CULTURE

(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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