PIK3CA Mutational Analysis of Parathyroid Adenomas

Abstract

Benign parathyroid adenoma is the most common cause of primary hyperparathyroidism, whereas malignant parathyroid carcinoma is exceedingly rare. Distinguishing parathyroid carcinoma from benign adenoma is often difficult, and may be considerably delayed even after surgical resection until the rigorous diagnostic criteria of local invasion of surrounding tissues and/or distant metastases are fulfilled. Thus, new insights into their respective molecular bases may potentially aid in earlier diagnostic discrimination between the two, as well as informing new directions for treatment. In two recent studies, gain‐of‐function mutations in PIK3CA, a recognized driver oncogene in many human malignancies, have been newly identified in parathyroid carcinoma. To assess the potential specificity for malignant, as opposed to benign parathyroid disease, of PIK3CA hotspot mutations, we PCR‐amplified and Sanger sequenced codons 111, 542/545, and 1047 and the immediate flanking regions in genomic DNA from 391 typical, sporadic parathyroid adenomas. Four parathyroid adenomas (1%) had subclonal, somatic, heterozygous, activating PIK3CA mutations. The rarity of PIK3CA activating mutations in benign parathyroid adenomas suggests that tumorigenic activation of PIK3CA is strongly associated with malignant parathyroid neoplasia. However, it does not appear that such mutations, at least in isolation, can be relied upon for definitive molecular diagnosis of parathyroid carcinoma. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Somatic and Germline Mutations in Atypical Parathyroid Tumors

“…Likewise, mitochondrial gene mutations are known to be hallmarks of oxyphilic benign PAs, and we identified 1 APT sample with a mutation in MT-ND5 . PI3KCA was the only other gene mutated in multiple patient samples; both variants have been reported in benign PAs …”

“…3 PI3KCA was the only other gene mutated in multiple patient samples; both variants have been reported in benign PAs. 6 Limitations of this study include small sample size, limited follow-up, and the inherent subjectivity of APT diagnosis. The genetic background of APTs in this study is consistent with previous studies 3,4 of benign PAs, supporting the theory that APTs are predominantly benign rather than premalignant or intermediate tumors.…”

“…2,3 Despite the rise of alternative technologies, such as highspeed laryngoscopy and kymography, stroboscopic examination remains a mainstay tool for most laryngologists. [4][5][6] The current study aims to test whether a microcontroller can be used to construct an extremely low-cost stroboscope and assesses its strengths and weaknesses.…”

Biosensors for Point Mutation Detection

“…PIK3CA mutation is one of the most common mutations in human cancer. It has been identified as a biomarker of breast cancer ( Haefliger et al, 2020 ; Mollon et al, 2020 ), cervical cancer, endometrial cancer, ovarian cancer and parathyroid adenoma cancer ( Milano, 2020 ; Riccardi et al, 2020 ). Mutations in exon 9 and 20 of PIK3CA are closely related to colorectal cancer ( Jin et al, 2020 ).…”