Oncogene and growth factor expression in MEN 2 and related tumors

Area of Science:

• Endocrinology
• Oncology
• Molecular Genetics

Background:

• Pheochromocytomas and medullary thyroid carcinomas (MTCs) can arise sporadically or be associated with inherited syndromes like multiple endocrine neoplasia (MEN).
• The molecular genetic underpinnings of these endocrine tumors are not well understood.
• Previous research indicated frequent deletions on chromosome 1p in these tumors, suggesting a potential tumor suppressor gene.

Purpose of the Study:

• To investigate the structure and expression of specific oncogenes and growth factor-related genes in pheochromocytomas and MTCs.
• To determine the role of L-myc and other genes in the development of sporadic and hereditary forms of these endocrine tumors.

Main Methods:

• Southern blot analysis was used to examine gene structure (amplification, rearrangement, and loss of heterozygosity).
• Northern blot analysis and ribonuclease protection assays (RPA) were employed to assess gene expression at the RNA level.
• Radiolabeled DNA and cRNA probes were utilized for sensitive detection of genetic alterations and transcripts.

Main Results:

• No amplification or rearrangement of N-myc, c-myc, L-myc, c-mos, nerve growth factor (beta-NGF), or low-affinity nerve growth factor receptor (LNGFR) genes was found.
• Loss of heterozygosity at the L-myc locus (1p32) was observed in 9/9 MEN 2A/2B pheochromocytomas, 5/11 non-MEN pheochromocytomas, and 3/24 non-MEN MTCs.
• C-myc transcripts were detected at low levels in all tested tumor samples.

Conclusions:

• The L-myc gene, located at 1p32, is frequently affected by loss of heterozygosity in both sporadic and hereditary pheochromocytomas and MTCs.
• These findings support the hypothesis of a tumor suppressor gene on chromosome 1p, potentially L-myc, involved in the pathogenesis of these endocrine tumors.
• Further research is needed to elucidate the precise role of L-myc and other genetic factors in tumor development.