TY - JOUR
T1 - PIK3CA Mutational Analysis of Parathyroid Adenomas
AU - Riccardi, Aaliyah
AU - Lemos, Carolina
AU - Ramos, Ryan
AU - Bellizzi, Justin
AU - Parham, Kourosh
AU - Brown, Taylor C.
AU - Korah, Reju
AU - Carling, Tobias
AU - Costa-Guda, Jessica
AU - Arnold, Andrew
N1 - Publisher Copyright:
© 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - CANCER
KW - DISORDERS OF CALCIUM/PHOSPHATE METABOLISM
KW - PARATHYROID-RELATED DISORDERS
UR - http://www.scopus.com/inward/record.url?scp=85102483762&partnerID=8YFLogxK
U2 - 10.1002/jbm4.10360
DO - 10.1002/jbm4.10360
M3 - Article
C2 - 32537547
AN - SCOPUS:85102483762
SN - 2473-4039
VL - 4
JO - JBMR Plus
JF - JBMR Plus
IS - 6
M1 - e10360
ER -