Board Preparation: Cancer Genetics, Sarcoma

Jul 27, 2015

Every issue of ASCO Connection: Trainee & Early-Career Oncologists has an opportunity for you to test your knowledge in order to assist your preparations for Board examinations. Questions in this issue come from two popular courses on ASCO University: Cancer Genetics Program and Sarcoma Review.

Take a comprehensive approach to your Board preparations with the latest edition of ASCO-SEP®. Released in October 2014, the fourth edition features more than 180 self-assessment questions and 21 chapters that provide the most current information on all major cancer types, cancer prevention and epidemiology, the molecular biology of cancer, palliative care, symptom management, and geriatric care, as well as overviews of clinical pharmacology, biologic therapies, and statistics.

Correct answers are listed at the bottom of the page.

1. When comparing cancer susceptibility syndromes due to mutations in oncogenes and tumor suppressor genes, which of the following is true?

  1. Syndromes due to inherited mutations of oncogenes tend to be recessive.
  2. Syndromes due to inherited mutations of oncogenes are much more common than those due to tumor suppressor genes.
  3. Tumor suppressor gene mutations more commonly demonstrate genotype-phenotype correlations.
  4. Tumors with mutant oncogenes can more readily be targeted by small molecule–based therapies compared with those due to mutant tumor suppressor genes.
  5. Cancer susceptibility in children is rarely due to mutant oncogenes.

2. 55-year-old man presents with progressive pulmonary metastatic disease after receiving ifosfamide, doxorubicin, and mesna for metastatic synovial sarcoma. His disease responded initially, but incompletely.

Improvement in progression-free survival has been demonstrated for which of the following agents compared with placebo in a randomized prospective trial?

  1. Gemcitabine
  2. Docetaxel
  3. Sunitinib
  4. Imatinib
  5. Pazopanib

 

Rationales

1: D

Mutations in oncogenes can cause inherited cancer. Although less common than syndromes associated with inherited mutations in tumor suppressor genes, both syndromes may demonstrate dominant inheritance and genotype-phenotype associations, but oncogene-associated cancer syndromes are more readily targetable by therapies.

D is correct: Mutant oncogenes due to overexpression of membrane tyrosine kinases, for example, can be targeted with small molecules that bind to these receptors in place of natural ligand (e.g., RET, KIT). Both oncogene and tumor suppressor gene syndromes tend to be Mendelian dominant, and both can show genotype-phenotype correlations, thus A and C are incorrect. Cancer susceptibility is most often due to defects in tumor suppressor genes, thus B is incorrect. RET mutations causing thyroid cancer are an example of an oncogene tumor susceptibility syndrome in children, thus E is incorrect.

2: E

Pazopanib is approved for treatment of advanced and metastatic non-gastrointestinal stromal tumor, non-adipocyte soft tissue sarcoma after treatment with chemotherapy based upon a phase III placebo-controlled trial that showed that pazopanib significantly increased progression-free survival compared with placebo. A previous European Organisation for Research and Treatment of Cancer phase II study did not show benefit for nonselected adipocytic soft tissue sarcoma. With the inclusion of leiomyosarcomas, synovial sarcomas, and many other histologic types, the PALETTE study is relevant to most patients with soft tissue sarcoma.

Suggested Reading

van der Graaf WT, Blay JY, Chawla SP, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012;379:1879-86. PMID: 22595799.

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