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Cancer genetics
Short report
Novel truncating germline variant reinforces TINF2 as a susceptibility gene for familial non-medullary thyroid cancer
  1. Josep Oriola1,2,
  2. Orland Díez3,
  3. Mireia Mora4,5,
  4. Irene Halperin6,
  5. Sandra Martínez7,
  6. Miriam Masas8,
  7. Anna Tenes8,
  8. Anna Bernal9,
  9. Rafael Duran10,
  10. Aida Orois11
  1. 1 Biochemistry and Molecular Genetics Department, Hospital Clinic de Barcelona, Barcelona, Spain
  2. 2 Biomedicina, Universitat de Barcelona Facultat de Medicina i Ciencies de la Salut, Barcelona, Spain
  3. 3 Area of Clinical and Molecular Genetics. Cancer Genetics Group, Vall d'Hebron Institut d'Oncologia, Barcelona, Spain
  4. 4 Endocrinology and Nutrition Department. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic de Barcelona, Barcelona, Spain
  5. 5 Universitat de Barcelona Facultat de Medicina i Ciencies de la Salut, Barcelona, Spain
  6. 6 Endocrinology Department, ICMDM, Hospital Clinic de Barcelona, Barcelona, Spain
  7. 7 FED Endocrinologia y Nutrición, Hospital General de Elda, Elda, Spain
  8. 8 Vall d'Hebron University Hospital Clinic and Molecular Genetics Area, Barcelona, Spain
  9. 9 Biochemistry and Molecular Genetics, Hospital Clinic de Barcelona, Barcelona, Spain
  10. 10 Servicio de Patología, Hospital General de Elda, Elda, Spain
  11. 11 Endocrinology, ICMDM, Hospital Clinic de Barcelona, Barcelona, Spain
  1. Correspondence to Dr Josep Oriola; joriola{at}clinic.cat

Abstract

Background It has long been observed that there are families in which non-medullary thyroid cancer (NMTC) occurs, but few syndromes and genes have been described to date. Proteins in the shelterin complex have been implied in cancer. Here, we have studied shelterin genes in families affected by NMTC (FNMTC).

Methods We performed whole-exome sequencing (WES) in 10 affected individuals from four families with at least three affected members. Polymerase chain reaction (PCR) and Sanger sequencing were performed to search for variants in the TINF2 gene in 40 FNMTC families. TINF2 transcripts and loss of heterozygosity (LOH) were studied in several affected patients of one family.

Results We found the c.507G>T variant in heterozygosis in the TINF2 gene in one family, co-segregating in all five affected members. This variant affects the normal splicing. LOH was not observed.

Conclusions Our results reinforce the TINF2 gene as a susceptibility cause of FNMTC suggesting the importance of location of frameshift variants in TINF2. According to our data and previous literature, TINF2 pathogenic variants appear to be a significant risk factor for the development of NMTC and/or melanoma.

  • Endocrine Gland Neoplasms
  • Frameshift Mutation
  • Genetics, Medical
  • Genetic Testing
  • Germ-Line Mutation

https://doi.org/10.1136/jmg-2024-110185

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    Footnotes

    • Contributors JO: Conceptualisation (lead); formal analysis (lead); investigation (lead); resources acquired (equal), writing—original draft (supporting); writing—review and editing (equal). OD: Formal analysis (supportive); writing—review and editing (equal). MMo: Resources acquired (equal); writing—review and editing (equal). IH: Resources acquired (equal); writing—review and editing (equal). AB: Methodology (equal); writing—review and editing (equal). MMa: Methodology (equal); writing—review and editing (equal). AT: Methodology (equal); writing—review and editing (equal). SM: Investigation (supporting); writing—review and editing (equal). RD: Investigation (supporting); writing—review and editing (equal). AO: Conceptualisation (supporting); formal analysis (supporting); investigation (supporting); resources acquired (equal), writing—original draft (lead); writing—review and editing (equal).

    • Funding This work was funded by the Catalan Society of Endocrinology and Nutrition (Fellowship 2015/2016), Hospital Clínic de Barcelona (End-of-Residence Award 2016/2017) and The Spanish Society of Endocrinology and Nutrition (Beca Morreale-Escobar 2017/2018).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.