Genetic profile identification and clinicopathologic characteristics analysis of the thyroid-like low-grade nasopharyngeal papillary adenocarcinoma.

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA) is an extremely rare malignancy bearing histomorphological similarities to papillary thyroid carcinoma with good prognosis. It's important to distinguish TL-LGNPPA from other papillary tumors including nasopharyngeal papillary adenocarcinoma (NPPA), metastatic and ectopic papillary thyroid cancer, and metastasized adenocarcinomas, etc. To date, only 48 cases of TL-LGNPPA have been reported in the English literatures. Here, we reported the genomic characteristics of additional 4 cases and reviewed other reports to clarify the clinicopathological features of this tumor. In this study, 41 mutations were detected by whole-exome sequencing, but no typical driver mutations were found. Two sample with Copy Number Variations (CNV) were found (7 q22. 17 q12), of which the segment spanned the regions of RASA4, POLR2J2, SPDYE2, CCL3, CCL4, etc. Additionally, no MSI and HLA LOH were found. To our knowledge, we are the first to reveal the genetic underpinnings of this rare tumor. The clinicopathological features of TL-LGNPPA were characterized, shedding more light on the essential difference between TL-LGNPPA with other papillary tumors.

A BRCA1 Splice Site Variant Responsible for Familial Ovarian Cancer in a Han-Chinese Family.

OBJECTIVE: Ovarian cancer (OC) is one of the most common and most lethal gynecological malignancies. OC has an age-dependent incidence and occurs more commonly in females older than 50 years old. Most OC patients are diagnosed at an advanced stage and have a poor prognosis. Germline mutations in the BRCA1 DNA repair associated gene (BRCA1) and the BRCA2 DNA repair associated gene (BRCA2) account for 20%-25% of epithelial ovarian cancer (EOC). BRCA1 germline mutations are more common in Chinese EOC patients. METHODS: This study reported a three-generation Han-Chinese family containing four EOC patients and a rectal adenocarcinoma patient. Whole-exome sequencing was performed on two EOC patients and an unaffected individual. Variant validation was also performed in all available members by Sanger sequencing. RESULTS: A heterozygous splice site variant, c.4358-2A>G in the BRCA1 gene, was identified. Bioinformatic analysis showed that the variant may change the splicing machinery. CONCLUSION: The BRCA1 splice site variant, c.4358-2A>G was identified as the likely genetic cause for EOC, and may also be associated with the increased risk of rectal adenocarcinoma in the family. The findings were beneficial for genetic counseling, helpful for cancer prevention in other family members, and may facilitate therapy decision-making in the future to reduce cancer lethality.