miércoles, 19 de julio de 2017

Multifocal gastric adenocarcinoma in a patient with LRBA deficiency | Orphanet Journal of Rare Diseases | Full Text

Multifocal gastric adenocarcinoma in a patient with LRBA deficiency | Orphanet Journal of Rare Diseases | Full Text

Biomed Central



Orphanet Journal of Rare Diseases

Multifocal gastric adenocarcinoma in a patient with LRBA deficiency

  • Nina Bratanič,
  • Jernej Kovač,
  • Katka Pohar,
  • Katarina Trebušak Podkrajšek,
  • Alojz Ihan,
  • Tadej Battelino and
  • Magdalena Avbelj StefanijaEmail authorView ORCID ID profile
Orphanet Journal of Rare Diseases201712:131
DOI: 10.1186/s13023-017-0682-5
Received: 30 March 2017
Accepted: 7 July 2017
Published: 18 July 2017


Abstract

Background

Lipopolysaccharide-responsive, beige-like anchor protein (LRBA) deficiency is characterized by primary immunodeficiency and autoimmunity. Cancer may present another feature of LRBA deficiency. We describe a case history of a young adult with LRBA deficiency and two independent malignancies.

Methods

Family-trio whole exome sequencing with unbiased phenotype ontology approach was used for identification of causative mutations of a primary immune deficiency disorder. Additionally, we sought to identify germline mutations in genes known to be associated with two independent malignancies using a targeted approach. A cytotoxic T-lymphocyte associated protein 4 (CTLA4) expression in T lymphocytes was determined by flow cytometry.

Results

In the patient with clinical signs of LRBA deficiency multifocal gastric carcinoma and malignant melanoma were diagnosed and surgically treated at 19 and 27 years of age, respectively. Despite refusal of any adjuvant chemotherapy or radiotherapy, the patient demonstrated disease free survival for at least 13 years after the first cancer diagnosis. A homozygous frameshift deletion in LRBA gene (p.Glu946Ter) and two common variants in TYR gene were identified. Reduced CTLA4 expression in a subset of regulatory T lymphocytes was identified in the patient and his unaffected mother carrying a heterozygous LRBA mutation as compared to control in a dose-dependent manner.

Conclusion

This is the first description of gastric cancer and malignant melanoma in a young adult with LRBA deficiency. The role of LRBA gene knockout in cancer development and its prognosis remains to be elucidated.


Keywords

Lipopolysaccharide-responsive, Beige-like anchor (LRBA) Immunodeficiency Autoimmunity Gastric cancerMalignant melanoma Cytotoxic T-lymphocyte associated protein 4 (CTLA4) Malignancy

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