The impact of the genetic background in a patient with papillary thyroid cancer and familial adenomatous polyposis

Abstract

Thyroid cancer is the most common endocrine malignancy, and papillary thyroid carcinoma (PTC) is the main subtype. The cribriform morular variant is a histological phenotype of PTC characterized by its relationship with familial adenomatous polyposis (FAP). Description of the case: We report the genetic assessment of a 20-year-old female patient diagnosed with a cribriform-morular variant of PTC and FAP. We aimed to assess the genetic background of the reported patient, looking for variants that would help us explain the predisposition to tumorigenesis. Genomic DNA was extracted from peripheral blood lymphocytes, and whole exome sequencing was performed. We applied an overrepresentation and gene-set enrichment analysis to look for an accumulation of effects of variants in multiple genes at the genome. We found an overrepresentation of single nucleotide variants (SNVs) in extracellular matrix interactions and cell adhesion genes. Underrepresentation of SNVs in genes related to the regulation of autophagy and cell cycle control was also observed. We hypothesize that the package of alterations of our patient may help to explain why she presented colonic manifestations and thyroid cancer. Our findings suggest that multiple variants with minor impact, when considered together, may be helpful to characterize one particular clinical condition.

Cribriform Morular Thyroid Carcinoma: A Rare Case and Associated Uncommon Features

“…1,9 IHC features of the reported cases are mentioned in Table 1. 5,8,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] TTF1 will be strongly positive in the tumor cells in the nonmorular area. PAX8 is focal, with weak reactivity in some cells of the cribriform component while negative in the morular component.…”

Cribriform morular thyroid carcinoma: Clinicopathological and molecular basis for both a preventive and therapeutic approach for a rare tumor (Review)

“…More than 85% of germline APC mutations in patients with CMTC have been detected in exon 15 (codons 463 to 1,387), in the same genomic location usually associated with CHRPE ( 39 ). This area also includes a hotspot (codon 1,061) for CMTC and hepatoblastoma ( 25 , 35 , 37 , 39 ), but mutations in codons 140, 159, 161, 213, 278, 302, 313, 325, 332, 418, 471, 499, 554, 578, 582, 593, 625, 654, 698, 704, 737, 769, 778, 804, 834, 848, 935, 937, 938, 964, 976, 977, 979, 993, 1,062, 1,068, 1,073, 1,105, 1,110, 1,157, 1,275, 1,307, 1,309, 1,394, 1,465 and 2,092 have also been described ( 33 , 56 , 75 , 76 ). When comparing the prevalence of APC mutations in patients with FAP and TC in relation to the prevalence of such mutations in unselected individuals with FAP, a higher risk of CMTC exists in the population harboring APC mutations proximal to the 5′ end (proximal to codon 528) as well as in the established high-risk group with mutation at codon 1,061 ( 75 ).…”