University of Pittsburgh Cancer Institute (UPCI)

Genetic Susceptibility

DNA strand Certain genetic backgrounds or carcinogen-induced mutations may play a role in lung cancer development and progression. LCP members are working to identify and characterize these genetic changes, in order to develop effective diagnostic and prognostic markers.


Selected Publications

  • The significance of KRAS mutant allele-specific imbalance (MASI) in lung adenocarcinomas is unknown. KRAS MASI was defined as predominance of the mutant allele over the wild-type allele. LCP investigators assessed the frequency of KRAS MASI by comparing peak heights of mutant and wild-type alleles on sequencing electropherograms and by KRAS fluorescence in situ hybridization. KRAS MASI was associated with selective amplification of the KRAS mutant allele. Patients with KRAS MASI showed worse overall survival, and prognostic significance was independent of clinical stage. The detection of KRAS MASI in lung adenocarcinomas by sequencing electropherograms may identify patients with more aggressive disease (Chiosea SI, et. al., Mod Pathol. 24:1571-7, 2011).
  • Steroid hormones and growth factors affect lung cancer, and it is possible they act in concert to influence patient outcome. Primary lung tumors and normal lung tissue were analyzed for expression and localization of estrogen receptor α and ß-1 (ERα and ERß), aromatase, progesterone receptor (PR), and epidermal growth factor receptor (EGFR). Results show that hormonal and EGFR pathways together may contribute to lung cancer prognosis. Lung tumors with high ERß -1/low PR may define patients with aggressive biology (Stabile LP, et. al., Clin Cancer Res. 17:154-64, 2011).
  • Molecular testing of pulmonary adenocarcinomas for EGFR and KRAS mutations is becoming more common as tyrosine kinase inhibitor therapy is used for EGFR-mutated adenocarcinomas. Results show that EGFR mutations occur in adenosquamous carcinoma in the same percentages as in conventional adenocarcinoma in the Western population, but KRAS mutations are less common (Tochigi N, et. al., Am J Clin Pathol. 135:783-9, 2011).

Members

Becich, Michael, MD, PhD
Biomedical Informatics (DBMI)
Ortiz, Luis, MD
Environmental & Occupational Health
Dacic, Sanja, MD, PhD
Pathology
Stabile, Laura, PhD
Pharmacology & Chemical Biology
Day, Roger, ScD
Biomedical Informatics (DBMI)
Yousem, Samuel, MD
Pathology
Dhir, Rajiv, MD
Pathology