A novel heterozygous large deletion of MSH6 gene in a Chinese family with Lynch syndrome

Abstract Background Multiple genetic variations have been identified in mismatch repair genes for Lynch Syndrome. However, diagnosis of Lynch Syndrome and its subtypes in patients with atypical cancer types still remains challenging. Little is known about Lynch syndrome-related renal carcinoma and related genes. We present a case of renal carcinoma with multiple primary skin tumors, with a new Lynch Syndrome variant with a deletion in a Chinese family. Case presentation: The patient was a 60-year-old Chinese male with a history of Lynch Syndrome-related renal carcinoma with repeatedly multiple primary skin tumors. Immunohistochemistry revealed loss of MSH2 and MSH6 proteins. Sequencing of mismatch repair genes revealed a previously unknown germline MSH2 mutation (c.1024_1026 del) resulting in an amino acid deletion (p. V342del). This variant was co-segregated among the carcinoma-affected family members. After 6 cycles of immunotherapy, a marked regression of the skin tumor was obtained. Conclusions We clarify the pathogenic significance of this new mutation and suggest immunotherapy for patients with this subtype of Lynch Syndrome.

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Lynch syndrome-associated lung cancer: pitfalls of an immunotherapy-based treatment strategy in an unusual tumor type

Exploration of Targeted Anti-tumor Therapy ◽

10.37349/etat.2021.00044 ◽

2021 ◽

Author(s):

Elena Maccaroni ◽

Edoardo Lenci ◽

Veronica Agostinelli ◽

Valeria Cognigni ◽

Riccardo Giampieri ◽

...

Keyword(s):

Lung Cancer ◽

Lynch Syndrome ◽

Rectal Adenocarcinoma ◽

Brca2 Gene ◽

Tumor Type ◽

Variant Of Uncertain Significance ◽

Cancer Predisposition Syndrome ◽

Msh6 Gene ◽

Increased Risk ◽

Uncertain Significance

Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline alterations in mismatch repair (MMR) genes leading to increased risk of colon cancer as well as other cancer types. Non-small cell lung cancer (NSCLC) is not among typical Lynch syndrome-associated tumors: pembrolizumab, an immune checkpoint inhibitor, is actually approved for the treatment of NSCLC patients and represents a promising treatment option for patients with advanced metastatic MMR-deficient cancer, regardless of tumor origin. This case report describes the clinical presentation and management of a 74-year-old female with a history of rectal adenocarcinoma and ovarian cancer, who has a documented frameshift pathogenic variant in the exon 8 of MSH6 gene and an intronic variant in the BRCA2 gene (classified as a variant of uncertain significance), affected by NSCLC with brain metastases. Despite these premises, the patient was treated with pembrolizumab and she did not benefit from this kind of treatment.

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