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MG-107 Multiple pathogenic variants identified by next-generation sequencing hereditary cancer panel testing – a case report
  1. Christopher A Tan1,
  2. Marina Rabideau1,
  3. Stephanie Cohen2,
  4. Shan Yang1,
  5. Karen Vikstrom1,
  6. Federico A Monzon1
  1. 1Invitae, San Francisco, CA, USA
  2. 2St. Vincent Hospital, Indianapolis, IN, USA


Background The utilisation of next-generation sequencing technology to interrogate multiple genes simultaneously is being utilised more frequently in hereditary cancer testing. While this has benefits of reducing cost and allowing clinicians to cast a wide net in the elucidation of their patient’s cancer, panel testing has the potential to reveal unexpected information. We report on a proband with pathogenic variants in two different hereditary colon cancer syndromes.

Case report A 39 year-old male with history of colon cancer diagnosed at 38, with normal IHC, and >20 colon polyps presented for genetic counselling. Family history was significant for a paternal aunt and paternal uncle with colon cancer in their early 50s. Both parents reportedly had colon polyps requiring frequent colonoscopy; his mother had a TAH-BSO at 40 for unknown reasons. Testing with a 7-gene high-risk hereditary colon cancer panel identified a homozygous pathogenic variant, c.1187G >A (p. Gly396Asp), in MUTYH and a likely pathogenic duplication of exon 7 in MSH2. Due to this finding, his parents were referred for genetic counselling and testing; his mother, who was diagnosed with colon cancer in the interim, was found to carry the MSH2 duplication. Both parents were obligate carriers of the MUTYH variant.

Conclusion This case example demonstrates the impact of identifying multiple hereditary syndromes. Being aware of all conditions has significant impact on at-risk family members particularly those who test negative for a known familial pathogenic variant, yet could still be at risk for cancer due to a second familial pathogenic variant.

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