No abstract

11 deletion, corresponding to exons 6 to 37 of ATM, was identified in both siblings. Subsequent Sanger sequencing of ATM identified a second pathogenic variant [c.9091del; p.(Gln3031Lysfs*2)]. The diagnosis was also supported by abnormal chromosome breakage studies. Clinical laboratories should have clear and consistent reporting policies when determining the significance of deletions involving genes associated with autosomal recessive conditions. This case demonstrates how phenotypic information is critical in guiding what findings should be reported and what follow up testing should be considered if a diagnosis has not been established.

Aim: Mantle cell lymphoma (MCL), is characterised by the t(11;14). Detection of t(11;14) by FISH is used in diagnosis. Clinically significance of additional abnormalities remains unclear. Our aim was to use a comprehensive FISH panel to identify secondary changes in a retrospective cohort of MCL samples. Method: FISH was performed retrospectively on 28 FFPE lymph node samples from patients diagnosed with MCL. Lymph node punch biopsies were constructed into a tissue microarray of 10 samples per slide in duplicate. The FISH probe panel was designed to detect rearrangements of BCL6, MYC and BCL2 and copy number loss of ATM and TP53 and confirmation of the presence of the t(11;14). Result: At least one additional abnormality including losses of TP53 (5/26), ATM (11/26), polysomies for MYC (8/26), BCL6 (18/26) and BCL2 (10/26) and rearrangements of MYC (2/26) and BCL6 (1/26) was observed in 24/28 (86%) cases. Two or more additional changes were observed in 13/28 (46%) patients. One patient had triple-hit with rearrangements of CCND1, MYC and BCL6. Conclusion: Expansion of the FISH probe panel detected additional abnormalities in 26/30 (86%) of patients including a triple hit case. HERITABLE CANCER RISK IN THE GENOMIC ERA