Tumor Biology

, Volume 35, Issue 9, pp 9219–9227 | Cite as

Germline mutations of TP53 gene in breast cancer

  • Surekha Damineni
  • Vadlamudi Raghavendra Rao
  • Satish Kumar
  • Rajasekar Reddy Ravuri
  • Sailaja Kagitha
  • Nageswara Rao Dunna
  • Raghunadharao Digumarthi
  • Vishnupriya Satti
Research Article


Germline alterations of the TP53 gene encoding the p53 protein have been observed in the majority of families with the Li–Fraumeni syndrome, a rare dominantly inherited disorder with breast cancer. Genomic DNA samples of 182 breast cancer cases and 186 controls were sequenced for TP53 mutations in the exon 5–9 and intervening introns 5, 7–9. Direct sequencing was done using Applied Biosystem 3730 DNA analyzer. In the present study, we observed nine mutations in the sequenced region, of which five were novel. Hardy-Weinberg equilibrium (HWE) was done for all the mutations; C14181T, T14201G, and G13203A have shown deviation from HWE. High linkage disequilibrium (LD) was observed between C14181T (rs129547788) and T14201G (rs12951053) (r 2 = 0.98.3; D′ = 1.00), whereas other observed mutations do not show strong LD with any of the other mutations. None of the intronic mutations has shown significant association with the breast cancer, two exonic mutations G13203A (rs28934578) and A14572G are significantly (P = 0.04, P = 0.007) associated with breast cancer. Germline mutations observed in DNA-binding domain of the gene showed significant association with breast cancer. This study reports five novel germline mutations in the TP53 gene out of which one mutation may confer significant risk to the breast cancer. Mutations in DNA-binding domain of TP53 gene may play role in the early onset and prognosis of breast cancer. The population-based studies of germline mutations in DNA-binding domain of TP53 gene helps in identification of individuals and families who are at risk of developing cancers.


TP53 Mutations DNA-binding domain Breast cancer 



I would like to acknowledge the University Grants Commission (U.G.C) New Delhi, India, Department of Medical Oncology, Nizams Institute of Medical Sciences, Hyderabad, India for the financial assistance. I would like to thank the Anthropological survey of India, Mysore, India for providing sequencing facility and necessary consumables and Mr. Jagan Mohan Rao Allu for his help in structural analysis.


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Surekha Damineni
    • 1
  • Vadlamudi Raghavendra Rao
    • 2
  • Satish Kumar
    • 2
  • Rajasekar Reddy Ravuri
    • 2
  • Sailaja Kagitha
    • 1
  • Nageswara Rao Dunna
    • 1
  • Raghunadharao Digumarthi
    • 3
  • Vishnupriya Satti
    • 1
  1. 1.Department of GeneticsOsmania UniversityHyderabadIndia
  2. 2.Anthropological Survey of India, Government of IndiaKolakataIndia
  3. 3.Department of Medical OncologyNizams Institute of Medical SciencesHyderabadIndia

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