De novo familial adenomatous polyposis associated thyroid cancer with a c.2929delG frameshift deletion mutation in APC: a case report and literature review

Abstract

Background Germline mutations in the APC gene located on chromosome 5q 21–22 can lead to familial adenomatous polyposis (FAP) and the development of colorectal cancer (CRC) if left untreated. As a rare extracolonic manifestation, thyroid cancer is diagnosed in about 2.6% of FAP patients. The genotype–phenotype correlation in FAP patients with thyroid cancer remains unclear. Case presentation We present a 20-year-old female of FAP with thyroid cancer as the initial manifestation. The patient was asymptomatic and developed colon cancer liver metastases 2 years after the diagnosis of thyroid cancer. The patient underwent multiple surgical treatments in several organs, and regular colonoscopy with endoscopic polypectomy was performed. Genetic testing demonstrated the c.2929delG (p.Gly977Valfs*3) variant in exon 15 of the APC gene. This represents a previously undescribed APC mutation. This mutation causes loss of multiple structures on the APC gene including the 20-amino acid repeats, the EB1 binding domain, and the HDLG binding site, which may be pathogenic through β-catenin accumulation, cell cycle microtubule dysregulation, and tumor suppressor inactivation. Conclusions We report a de novo FAP case with thyroid cancer presenting atypically aggressive features harboring a novel APC mutation and review APC germline mutations in patients with FAP-associated thyroid cancer.

Genetic Predisposition to Differentiated Thyroid Cancer among Polish Population

“…Even though in most cases papillary thyroid carcinoma associated with FAP occurs in females in their 30s and rarely in the elderly, there are several cases described where the disease occurred among patients in other age groups, as well as among members of the same family. As a rare extracolonic manifestation of the FAP, thyroid cancer, not solely PTC, is diagnosed in about 2.6% of all FAP patients globally, however the molecular background of this malignancy remains unknown [69,70]. The most significant variants occurring more frequently among Polish population (see Table S1) are missense variants of conflicting interpretation of pathogenicity.…”

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 ).…”

“…While most cases of familial CMTC are multifocal (and bilateral) at diagnosis, most sporadic cases present as single nodules ( 5 , 26 , 31 ). Because congenital hypertrophy of the retinal pigment epithelium (CHRPE) is reported to occur in up to 80% of individuals with FAP ( 32 , 33 ), and ophthalmoscopic examination can help to clinically confirm hereditary cases of CMTC ( 34 ).…”

“…In addition to colorectal adenomatous polyps and cancer ( 33 – 35 ), the coexistence of TC with medulloblastoma ( 36 ), stomach polyps ( 37 ), duodenal polyps ( 36 , 38 ), ampullary neoplasms ( 25 , 37 ), hepatoblastoma ( 39 ), adrenal adenoma ( 25 ), endometrial cancer ( 40 ), osteomas ( 35 ), lipomas ( 35 ), sebaceous and epidermoid cysts ( 35 ), desmoid tumors ( 25 , 35 , 38 ) as well as bilateral breast fibromatosis in the context of silicone prosthetics ( 41 ) have been described in patients with FAP.…”

Exploring the oral‐gut microbiota during thyroid cancer: Factors affecting the thyroid functions and cancer development

“…MEN2b is a modularized TC connected with benign tumors that develop in the tongue and nerve tissues elsewhere in the body, again named pheochromocytomas and neuroma. Moreover, hereditary diseases (such as Gardner syndrome, Cowden's disease, and familial adenomatous polyposis) also act as risk factors for TC (Punatar et al, 2012 ; Xu et al, 2023 ).…”