Early Onset Multiple Primary Tumors in Atypical Presentation of Cowden Syndrome Identified by Whole-Exome-Sequencing

Frontiers in Genetics
Mathias CavailléYves-Jean Bignon

Abstract

A family with an aggregation of rare early onset multiple primary tumors has been managed in our oncogenetics department: the proband developed four early onset carcinomas between ages 31 and 33 years, including acral melanoma, bilateral clear cell renal carcinoma (RC), and follicular variant of papillary thyroid carcinoma. The proband's parent developed orbital lymphoma and small intestine mucosa-associated lymphoid tissue (MALT) lymphoma between 40 and 50 years old. Whole-exome-sequencing (WES) of the nuclear family (proband, parents, and sibling) identified in the proband a de novo deleterious heterozygous mutation c.1003C > T (p.Arg335∗) in the phosphatase and tensin homolog (PTEN) gene. Furthermore, WES allowed analysis of the nuclear family's genetic background, and identified deleterious variants in two candidate modifier genes: CEACAM1 and MIB2. CEACAM1, a tumor suppressor gene, presents loss of expression in clear cell RC and is involved in proliferation of B cells. It could explain in part the phenotype of proband's parent and the occurrence of clear cell RC in the proband. Deleterious mutations in the MIB2 gene are associated with melanoma invasion, and could explain the occurrence of melanoma in the proband. Cowden ...Continue Reading

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Citations

Feb 29, 2020·Genes·K M Tahsin Hassan Rahit, Maja Tarailo-Graovac
Aug 19, 2020·World Journal of Surgical Oncology·Sofia MigueloteJ P Araújo Teixeira
Oct 22, 2020·NPJ Genomic Medicine·Raymond H KimCharis Eng
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Mar 22, 2020·Annales de pathologie·Virginie VerkarreStéphane Richard

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Methods Mentioned

BETA
exome-sequencing
Exome Sequencing
ubiquitination

Software Mentioned

BaseRecalibrator
PrimerBlast
Seqman
Human Splice Finder (
ALAMUT ( Interactive BioSoftware )
GATK HaplotypeCaller
bcl2fastq2 Conversion
Polyphen
Eurogenetest
PICARD

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