Test Code: 9790C

CEN4GEN Comprehensive Hereditary Cancer Syndrome: Sequencing Panel
Test Code: 9790C
Turnaround time: 3 to 4 weeks

CONDITION DESCRIPTION
This is a comprehensive predisposition screen for the following hereditary cancers:

Cancers:
Bloom Syndrome: BLM
Carney Complex: PRKAR1A
Costello Syndrome: HRAS
Cowden Syndrome: AKT1, PIK3CA, PTEN
Fanconi Anemia: BRCA2, BRIP1, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, PALB2, SLX4 (BTBD12)
Hereditary Desmoid Disease: APC
Li-Fraumeni Syndrome: CHEK2 (RAD53), TP53
LIG4 Syndrome: LIG4
Lynch Syndrome: EPCAM, MLH1, MSH2, MSH6, PMS2
Mismatch Repair Cancer Syndrome: MLH1, MSH2, MSH6, PMS2
Mosaic Variegated Aneuploidy: BUB1B
Seckel Syndrome 1: ATR
von Hippel-Lindau Syndrome: VHL

Bone Cancers:
Familial Osteosarcoma: TP53
Hereditary Bone Dysplasia with Malignant Fibrous Histiocytoma: MTAP
Multiple Exostoses: EXT1, EXT2
Rothmund-Thompson Syndrome: RECQL4

Colorectal Cancers:
Hereditary Adenomatous Polyposis: APC, MUTYH
Hereditary Colorectal Cancer: GALNT12, MLH3
Oligodontia-Colorectal Cancer Syndrome: AXIN2
POLD1 & POLE Associated Colorectal Adenomas: POLD1, POLE

Breast/Ovarian Cancers:
Hereditary Breast-Ovarian Cancer: BARD1, BRCA1, BRCA2, CHEK2 (RAD53), RAD51B (RAD51L1), RAD51C, RAD51D (RAD51L3)

Endocrine Cancers:
Hereditary Adrenal Pheochromocytoma: MAX, TMEM127, VHL
Hereditary Primary Pigmented Nodular Adrenocortical Disease: PDE11A, PRKAR1A
Hereditary Adrenocortical Cancer: TP53
Hereditary Adrenal Hyperplasia: CYP21A2
Hereditary Isolated Pituitary Adenoma: AIP
Hereditary Thyroid Cancer: NDUFA13, NTRK1, RET
Hyperparathyroidism-Jaw Tumor Syndrome: CDC73
Multiple Endocrine Neoplasia: CDKN1B (p27KIP1), MEN1
Pallister-Hall Syndrome: GLI3

GI Tract Cancers:
Bannayan-Riley-Ruvalcaba Syndrome: PTEN
Hereditary Barrett Esophagus/Esophageal Adenocarcinoma: ASCC1, MSR1
Hereditary Gastric Carcinoma: CDH1
Hereditary GIST: KIT (CD117), PDGFRA, SDHC
Howel-Evans syndrome: RHBDF2
Juvenile Polyposis Syndrome: BMPR1A (ALK3), SMAD4
Peutz-Jeghers Syndrome: STK11 (LKB1)

Hematopoietic Cancers:
Ataxia Telangetasia: ATM
Ataxia Telangetasia-like Disorder: MRE11A
Chediak-Higashi Syndrome: LYST
Familial Monocytic Leukemia: GATA2
Hereditary Acute Myeloid Leukemia: CEBPA, RUNX1 (AML1)
Hereditary Hodgkin Lymphoma: KLHDC8B
Nijmegen Breakage Syndrome: NBN (NBS1)
Nijmegen Breakage-like Syndrome: RAD50
Schwachman-Diamond Syndrome: SBDS
TERT Mutation-Associated Haematological Disorders: TERT
Wiskott-Aldrich Syndrome: WAS

Head & Neck Cancers:
Dyskeratosis Congenita: DKC1, RTEL1, TERT, TINF2
Hereditary Cylindromatosis: CYLD
Tuberous Sclerosis: TSC1, TSC2

Kidney Cancers:
Birt-Hogg-Dube Syndrome: FLCN
Denys-Drash Syndrome: WT1
Hereditary Leiomyomatosis & Renal Cell Cancer: FH
Hereditary Melanoma & Renal Cancer: MET, MITF
Hereditary Wilms’ Tumor: POU6F2, WT1
Perlman Syndrome: DIS3L2

Liver Cancers:
Hemochromatosis: HFE
Porphyria Cutanea Tarda: UROD
Tyrosinemia: FAH

Nervous System Cancers:
Carney-Stratakis Syndrome: PRKAR1A, SDHAF2, SDHB, SDHD
Hereditary Medulloblastoma: SUFU
Hereditary Neuroblastoma: ALK, KIF1B, PHOX2B
Hereditary Paragangliomas: SDHA
Neurofibromatosis: NF1, NF2
Retinoblastoma: RB1
Rhabdoid Predisposition Syndrome: SMARCA4, SMARCB1
Schwannomatosis: SMARCB1
Simpson-Golabi-Behmel Syndrome: GPC3

Skin Cancers:
Basal Cell Nevus Syndrome: PTCH1, PTCH2
Birt-Hogg-Dube Syndrome: FLCN
Familial Multiple Glomus Tumors: GLMN
Familial Multiple Trichoepithelioma: CYLD
Familial Uveal Melanoma: BAP1
Ferguson-Smith Syndrome: TGFBR1 (ALK5)
Hereditary Epidermodysplasia Verruciformis: TMC6, TMC8
Hereditary Leiomyomatosis & Renal Cell Cancer: FH
Hereditary Malignant Melanoma: CDK4, CDKN2A (p16INK4), MC1R, MITF, XRCC3
Muir-Torre Syndrome: MSH2
Palmoplantar Keratoderma & Squamous Cell Carcinoma: RSPO1
Xeroderma Pigmentosum: DDB2, ERCC2 (XPD), ERCC3 (XPB), ERCC4, ERCC5, ERCC6, POLH, XPA, XPC

Soft Tissue Cancers:
Hereditary Infantile Hemangioma: ANTXR1, KDR (VEGFR3)
Juvenile Hyaline Fibromatosis: ANTXR2
Opitz Trigonocephaly Syndrome: CD96
Proteus Syndrome: PTEN
SC Phocomelia Syndrome: ESCO2
Werner Syndrome: WRN

Other Cancers:
Familial Pancreatic Cancer: BRCA2, PALB2, PALLD
Hereditary Pleuropulmonary Blastoma: DICER1
Hereditary Prostate Cancer: BRCA2, EHBP1, EPHB2, MSMB, MSR1, RNASEL

INDICATIONS
The test is indicated for:

  • Individuals with a clinical or suspected diagnosis of an inherited cancer syndrome based on personal or family history of cancer.

 GENES

AIP, AKT1, ALK, ANTXR1, ANTXR2, APC, ASCC1, ATM, ATR, AXIN2, BAP1, BARD1, BLM, BMPR1A (ALK3), BRCA1, BRCA2, BRIP1, BUB1B, CD96, CDC73, CDH1, CDK4, CDKN1B (p27KIP1), CDKN2A (p16INK4), CEBPA, CHEK2 (RAD53), CYLD, CYP21A2, DDB2, DICER1, DIS3L2, DKC1, EHBP1, EPCAM, EPHB2, ERCC2 (XPD), ERCC3 (XPB), ERCC4, ERCC5, ERCC6, ESCO2, EXT1, EXT2, FAH, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, FH, FLCN, GALNT12, GATA2, GLI3, GLMN, GPC3, HFE, KDR (VEGFR3), KIF1B, KIT (CD117), KLHDC8B, LIG4, LYST, MAX, MC1R, MEN1, MET, MITF, MLH1, MLH3, MRE11A, MSH2, MSH6, MSMB, MSR1, MTAP, MUTYH, NBN (NBS1), NDUFA13, NF1, NF2, NTRK1, PALB2, PALLD, PDE11A, PDGFRA, PHOX2B, PIK3CA, PMS2, POLD1, POLE, POLH, POU6F2, PRKAR1A, PTCH1, PTCH2, PTEN, RAD50, RAD51B (RAD51L1), RAD51C, RAD51D (RAD51L3), RB1, RECQL4, RET, RHBDF2, RNASEL, RSPO1, RTEL1, RUNX1 (AML1), SBDS, SDHA, SDHAF2, SDHB, SDHC, SDHD, SLX4 (BTBD12), SMAD4, SMARCA4, SMARCB1, STK11 (LKB1), SUFU, TERT, TGFBR1 (ALK5), TINF2, TMC6, TMC8, TMEM127, TP53, TSC1, TSC2, UROD, VHL, WAS, WRN, WT1, XPA, XPC, XRCC3

METHODOLOGY

Next Generation Sequencing: In-solution hybridization of the regions encompassing full exonic gene sequences is performed on the patient’s genomic DNA. Direct sequencing of the captured regions is performed using next generation sequencing (NGS). The patient’s gene sequences are then compared to a standard reference sequence.  All sequence variants are evaluated using current scientific data to identify pathogenic, likely pathogenic variants, variants of unknown significance (VOUS) and carrier status.  Benign and likely benign variants are identified and classified using the latest published, scientific data are not listed in the report.  Variants of unknown significance (VOUS) that are either synonymous or outside coding regions are classified as likely benign.

DETECTION

Next Generation Sequencing: Clinical Sensitivity: Pathogenic variants in regions other than the targeted area, including the promoter region, some mutations in the introns and other regulatory element mutations, cannot be detected by this analysis. Large deletions/duplications will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient’s clinical/biochemical phenotype.

Analytical Sensitivity: ~99%.

SPECIMEN REQUIREMENTS

Submit only 1 of the following specimen types

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) or ACD (yellow top) tube: 5 ml
Specimen Collection and Shipping: Ship sample at room temperature with overnight delivery.

Type: Saliva Specimen
Requirements: Oragene™ kit (available from CEN4GEN)
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.