Thyroid Cancer Mutational Landscape

Differentiated thyroid cancer (DTC) comprises the papillary thyroid cancer (PTC) and the follicular thyroid cancer (FTC), making up more than 90% of cases of thyroid cancer. For reasons that are not fully understood, the incidence of DTC has seen a remarkable increase. In Saudi Arabia, DTC is quite common, ranking the fourth most common among all types of cancer and the second most common in females after breast cancer. Studies on genetic alterations in thyroid cancer in Saudi Arabia are limited. There has not been any study that comprehensively assesses the mutational profile of DTC and the association between gene mutations and the histopathological features and course of the disease.

We are planning to study a large sample of 3000 Saudi patients with DTC for the presence of mutations/gene rearrangements in BRAF, RAS, PIK3CA, PTEN, RET/PTC1 and RET/PTC3. In FTC cases, we will test for the presence of RAS mutations and PAX8/PPARy rearrangements.

A selection of 3000 consecutive cases between 1998 - 2024 will allow for a long follow-up time, enabling us to study long-term patient outcomes and the relationship with various gene mutations. DNA and RNA isolated from tumour tissue will be used to identify the mutations above via PCR amplication, direct sequencing and RT-PCR, and we will study the associations between mutations/gene arrangements and the histopathological features, recurrence and mortality.

Our approach is as follows: 1. Selection of 3000 consecutive cases seen in the years 1998-2024. This will allow a long follow-up time enabling us to study the long-term outcome of these patients and its relationship with the gene mutations 2.DNA and RNA isolation from tumor tissues carefully selected by a pathologist from formalin-fixed paraffin embedded tumor tissue 3.PCR amplification and direct sequencing of the exons that have been previously reported to contain point mutations in any of the above genes 4.Reverse transcription/polymerase chain reaction (RT-PCR) followed by direct sequencing for the gene rearrangements (RET/PTC and PAX8/PPARy) 5. Since mutations are usually mutually exclusive, we will exclude any case that has mutation/gene rearrangement from further testing. 5. Study the associations between mutations/gene rearrangements and the histopathological features, recurrence and mortality.