Oncology Diseases

The Anaplastic Lymphoma Kinase (ALK) gene is responsible for the synthesis of ALK receptors, which are especially important for the development of brain and nerve cells. ALK (2p23) gene rearrangements are observed in anaplastic large-cell lymphoma (ALCL), a systemic T-cell derived non-Hodgkin lymphoma type. In 75% of patients, t(2;5)(p23;q35) occurring between the ALK and NPM gene regions is detected and is associated with a poor prognosis. It has been associated with abnormal cell proliferation in non-small cell lung cancer (NSCLC). In the presence of an ALK mutation, the response to ALK TKI treatment in metastatic NSCLC patients is 50-61%.

Mutations that predispose to breast cancer are mainly in the BRCA1 and BRCA2 genes.

In normal cells, these genes help maintain DNA stability and prevent uncontrolled cell growth. They are therefore tumor suppressor genes. If a woman carries a dangerous mutation in the BRCA1 or BRCA2 gene, her lifetime risk of developing breast and/or ovarian cancer is greatly increased.

Breast or ovarian cancer occurs in 70-90% of carriers of BRCA 1-2 gene mutations. BRCA gene testing in family members suspected of hereditary breast cancer can confirm this condition.

The BRAF gene encodes a protein with serine/threonine kinase activity that plays a role in the mitogen-activated protein kinase signaling pathway (MAPKs). It exerts its effect through KRAS to control cell division. Somatic BRAF gene mutations have been detected in 15% of colorectal cancers (CRC) and 45% of papillary thyroid cancer. The most frequent mutation observed in carcinogenesis is V600E.

In Non-Small Cell Lung Cancer (NSCLC) cases that do not respond to treatment, screening for EGFR gene mutations and changing the treatment approach gains importance. The EGFR gene is located on the short arm of chromosome 7 (7p12) and consists of 28 exons. Somatic mutations are frequently detected in exons 18, 19, 20 and 21 located within the EGFR gene tyrosine kinase domain (exons 18-24), most frequently in exon 19 (46-50%), 21 (40-42%), 20 (6-7%), 18 (4-6%) and rarely in exon 22.

KRAS, the most common gene mutation, is routinely tested in all colon cancer patients.

In colorectal cancers (CRC), somatic KRAS and NRAS mutations that cause resistance to anti-EGFR therapies are observed at a rate of 30-40%, in non-small cell lung cancers (NSCLC) at 10-30%, in pancreatic cancers at 90%, and in head and neck tumors at 5%.

Mutations occurring in the TP53 gene cause breast cancer, soft tissue cancer and bone cancer. The TP53 gene is characterized by 2 autosomal dominant forms associated with cancer predisposition. These are classic Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-like (LFL) Syndrome, which manifest themselves with soft tissue sarcoma, osteosarcoma, breast cancer in the premenopausal period, brain tumors and adrenocortical carcinoma.

Multiple endocrine neoplasia type 2 (MEN2) can cause three different clinical pictures: MEN2A, FMTC (familial medullary thyroid carcinoma) and MEN2B. In all of them, the risk of medullary thyroid cancer is high. In addition, the risk of developing pheochromocytoma is increased in MEN2A and MEN2B. In MEN 2A cases, the risk of parathyroid adenoma and hyperplasia increases. The only genetic region known to cause MEN2 syndrome is the RET gene. With molecular genetic tests, mutations are identified in 98% of MEN2A and MEN2B cases, while this rate is 95% in FMTC cases. In our laboratory, the RET gene is studied as whole gene DNA sequencing.

Microsatellite instability is a genetic pathway responsible for approximately 15% of sporadic colon cancers. It occurs due to defects in the DNA mismatch repair system. In people with a defective DNA mismatch repair system, microsatellite instability occurs and the risk of mutation increases. These mutations occurring in tumor suppressor genes lead to the development of malignancies, especially colorectal cancer, as well as endometrial cancer, gastric cancer, etc. Microsatellite instability is most frequently detected in proximal colon cancers. Microsatellite instability in cancer tissues can be detected by the PCR method.

NTRK gene fusions involving NTRK1, NTRK2 or NTRK3 (encoding the neurotrophin receptors TRKA, TRKB and TRKC, respectively) are oncogenic drivers of various adult and pediatric tumor types. These fusions can be detected in the clinic using various methods such as tumor DNA and RNA sequencing and plasma cell-free DNA profiling. Treatment of patients with NTRK fusion-positive cancers with first-generation TRK inhibitors such as larotrectinib or entrectinib is associated with high response rates (>%75) regardless of tumor histology. First-generation TRK inhibitors are well tolerated by most patients, with toxicity profiles characterized by occasional non-tumor, target-directed adverse events (attributable to TRK inhibition in non-malignant tissues). Despite durable disease control in many patients, advanced NTRK fusion-positive cancers eventually become resistant to TRK inhibition; resistance can be acquired through the acquisition of NTRK kinase domain mutations. It can also be studied with real-time or NGS methods.

PD-L1 is a molecule that suppresses the activation of the immune system's T cells and causes tumors to progress. In cancers such as lung, stomach, liver, kidney, esophagus, pancreas, ovarian and bladder cancer, overexpression (positivity) of PD-L1 is known to be associated with poor clinical outcomes, while in breast cancer it is associated with better clinical outcomes. The prognostic value of PD-L1 expression in colorectal cancer and melanoma is debatable. Therefore, for example, other biomarkers (such as MSI, TML) are more prominent for colorectal cancers.

Studies show that the level of PD-L1 in tumor cells can guide treatment (immunotherapy) selection. Although it varies depending on the type of cancer and the organ of origin, patients with PD-L1 positive tumors give 2-3 times higher objective responses to immune checkpoint inhibitor drugs than negative ones.

The BCR-ABL1 fusion emerges after the breakage of the ABL1 gene located in the 9q34 region from a region close to its 5' portion, and the fusion of the remaining 3' fragment with the BCR gene on 22q11, broken from a region close to its 3' portion. The new chimeric gene that emerges after the translocation causes the production of an ABL1 protein (p210 fusion protein) with increased tyrosine kinase activity.