MEN Genetics

  1. What does a functional tumor mean?
    Capable of elaborating hormonal products that result in specific clinical findings characteristic of the hormone excess state
  2. Characteristics of MEN1?
    Tumors involving the parathyroid glands, endocrine pancreas and the pituitary
  3. Medullary carcinoma of the thyroid, phenochromocytoma, hyperparathyroidism are seen in MEN____
  4. T/F: hyperparathyroidism is absent in MEN2A but present in MEN2B
    False; it is present in 2A but absent in 2B. Remember the “P’s.” 2B has pheochromocytoma, and medullary carcinoma without hyperparathyroidism
  5. The 3P’s in MEN____ are:
    • MEN1
    • Parathyroid hyperplasia
    • Pituitary adenoma
    • Pancreatic tumor
    • (no pheochromocytoma)
  6. The 2P’s and 1M in MEN ____ are:
    • Parathyroid hyperplasia
    • Pheochromocytoma
    • Medullary Thyroid carcinoma
  7. The 1P and 2M in MEN_____ are:
    • Marfanoid body/ Mucosal neuroma
    • Medullary thyroid carcinoma
    • Pheochromocytoma
    • (no parathyroid hyperplasia)
  8. MEN1’s parathyroid hyperplasia is _______. Vs MEN2A’s parathyroid hyperplasia is ______.
    • Parathyroid tumors, hyperparathyroidism- MEN1
    • Hyperplasia of parafollicular cells, elevated calcitonin- MEN2A
  9. T/F: Cause of MEN 1 is adrenal hyperplasia, leading to adrenal adenoma
    False; it is hyperplasia of parathyroid, leading to parathyroid adenoma
  10. T/F: 95% of hyperparathyroidism is hereditary and usually caused by MEN1 or MEN2
    False; 95% of hyperparathyroidism is sporadic, non-hereditary, and of 50% of sporadic results from somatic mutations of MEN1. Only 5% of it is caused by hereditary MEN1 or MEN2A.
  11. Most common feature of MEN 1 is_____
  12. Malignant gastrinomas can be seen in patients with MEN___
    • 1
    • Enteropancreatic tumors are seen in 50% of MEN1
  13. Inheritance pattern of MEN1?
    • Autosomal Dominant (At the phenotype and pedigree level)
    • 10% de novo
  14. MEN1 encodes _____, which is a tumor _____. This is a _____ (LOF/GOF) mutation
    • Menin
    • Tumor suppressor
    • Loss of function. (leads to deregulated cell growth)
  15. T/F: the two-hit hypothesis applies to MEN 1, meaning one allele of MEN 1 is inactivated in every cell through germline mutation, it is then susceptible to additional random somatic mutations that will knock out the second allele
    True; the gene is genetically recessive but phenotypically dominant
  16. T/F: In sporadic hyperparathyroidism caused by MEN1 mutations, since it is autosomal dominant, therefore if there is mutation in one of the two alleles of MEN1 tumor suppressor gene, phenotypically, the person would be affected
    False; the gene itself is happlosufficient, so affecting one of the two alleles will have no change in phenotype because the second allele will act as a backup.
  17. T/F: Sporadic hyperparathyroidism is indicative of MEN1
    False; Although sporadic hyperparathyroidism is caused by MEN1 gene mutation, however, this mutation affects only one out of the four parathyroid glands vs MEN1 syndrome is 1 allele of MEN1 inactivated in every cell in all four parathyroids
  18. T/F: hereditary MEN1 syndrome (non-sporadic) is mutation that occurs in somatic cells.
    False; it is germline mutation
  19. _____ is a genetic predisposition in which 1 allele of MEN1 is inactivated in every cell in all four parathyroid, whereas _____ can randomly happen to anyone and only affects one of the 4 glands
    • MEN 1 syndrome
    • Sporadic hyperparathyroidism
  20. Inheritance pattern for MEN2?
    Autosomal dominant
  21. What is the most common and often first manifestation of MEN2?
    Medullary thyroid carcinoma
  22. What is Medullary thyroid carcinoma?
    Hyperplasia of calcitonin-producing parafollicular cells
  23. T/F: 80% of medullary thyroid carcinoma due to inherited causes is found in MEN2B
    False; it is found in MEN2A. MEN2B attributes to 5% of MTC
  24. What genetic mutation should patient with medullary thyroid carcinoma be screened for?
    RET – which is the genetic cause of MEN2, a gain of function proto oncogene
  25. Which of the MEN2 is more severe?
    MEN2B (MTC can metastasize)
  26. Which of the MEN2 is more prevalent?
  27. What is the RET gene? GOF/LOF? Inheritance pattern?
    Receptor tyrosine kinase, proto-oncogene, gain of function mutation and it is autosomal dominant
  28. Which MEN syndrome will have body type with long arms, legs and fingers, and bumps on lips, eyelids and tongue?
    MEN2B- marfanoid habitus/ mucosal neuroma
  29. T/F: MEN2 syndrome are caused by the MEN2 gene
    False; it is caused by gain of function mutation in RET
  30. What is MEN?
    • Genetic predisposition for tumors in multiple endocrine glands
    • Multiple Endocrine Neoplasias
    • All men are autosomal dominant
Card Set
MEN Genetics
Endo Exam 2