LYNCH SYNDROME

NEXT GENERATION SEQUENCING BASED TESTING FOR LYNCH SYNDROME

MUTATION TESTED: MLH1, MSH6, MSH2, PMS2 (primarily)

INDICATIONS FOR ORDERING:

Bethesda criteria were revised in 2004 to guide selection of patients for MSI testing . The guideline indicated that tumors should be tested for MSI in the following clinical situations:

• CRC diagnosed in a patient who is less than 50 years of age.
• Presence of synchronous, metachronous colorectal, or other LS-associated tumors, regardless of age.
• CRC with the MSI-H histology diagnosed in a patient who is less than 60 years of age.
• CRC diagnosed in one or more first-degree relatives with an LS-related tumor, with one of the cancers being diagnosed under age 50 years.
• CRC diagnosed in two or more first- or second-degree relatives with LS-related tumors, regardless of age.
• Patients with suspected hereditary CRC should be referred for genetic counseling, where the identification of germline mutations and evaluation/screening of family members can be appropriately addressed.
• Families that meet the Amsterdam Criteria (15) but who lack a germline mutation in an MMR gene and an MSI-H tumor, have been termed familial CRC.

METHOD USED:  Next Generation Sequencing (NGS) using a customised gene panel provided by ThermoFischer Scientific (LifeTechnologies Inc, USA)

SPECIMENS – Type, storage and transport

• Type: Non-diluted peripheral blood sample/bone marrow aspirate in an EDTA (lavender) tube. Formalin fixed paraffin embedded tissue sections (Tissue block).PLEASE AVOID HEPARINATED BLOOD

Bone Marrow: Min. 3mL

Whole Blood: 3 mL

• Transport: Specimens must be received within 48 hours of collection
• Storage: Whole Blood or Bone Marrow. Separate specimens must be submitted when multiple tests are ordered.
• Extracted DNA: Separate specimens must be submitted when multiple tests are ordered.
• Unacceptable samples: Specimens collected in anticoagulants other than EDTA, haemolysed/clotted samples

TEST DESCRIPTION: This is a next generation sequencing based assay to detect mutations in the mismatch repair genes enlisted above. This assay is done using amplicon based sequencing on the Ion Torrent (LifeTechnologies, USA) PGM and/or S5 platform, with a gene panel prepared and provided by ThermoFischer Scientific  (LifeTechnologies, USA)

TURNAROUND TIME: 15 (fifteen) working days from receipt of sample

QUALITY ASSURANCE & COMPETENCY TESTING: Regular internal quality checks and intra-lab comparisons are performed to ensure accurate and precise results. Material Safety Data Sheets (MSDS) may be ordered upon request. Highly trained personnel performing this test undergo regular competency assessments and attend regular conferences and educational programs in order to stay upbeat with the newer advances in the biology and diagnostics of the disease in question.

ACCREDITATION: NOT IN NABL SCOPE