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Patterns of PIK3CA alterations in familial colorectal and endometrial carcinoma

Miina Ollikainen1, Annette Gylling, Marjut Puputti

  • 1Department of Medical Genetics, University of Helsinki, Helsinki, Finland.

International Journal of Cancer
|May 2, 2007
PubMed

Insights

Alterations in PI3K pathway genes like PIK3CA, PTEN, and KRAS are common in familial colorectal and endometrial cancers. These genetic changes are crucial for understanding tumor development in these hereditary cancer syndromes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is frequently activated in sporadic cancers.
  • Its role in familial tumor development, particularly in colorectal (CRC) and endometrial carcinomas (EC), remains largely unexplored.
  • Understanding these alterations is key to deciphering hereditary cancer pathways.

Purpose of the Study:

  • To investigate the frequency and significance of alterations in PIK3CA, PTEN, and KRAS within the PI3K/AKT pathway.
  • To analyze these alterations in familial CRC and EC, stratified by DNA mismatch repair (MMR) gene mutation status.
  • To elucidate the role of PI3K pathway genes in the tumorigenesis of familial colorectal and endometrial cancers.

Main Methods:

  • Screening for PIK3CA, PTEN, and KRAS alterations in 160 familial CRC and EC samples.
  • Stratification of samples based on the presence or absence of germline mutations in MMR genes.
  • Statistical analysis to determine associations between genetic alterations and tumor characteristics.

Main Results:

  • PIK3CA alterations (mutations or amplification) were observed in 14% of CRCs and 21% of ECs.
  • PIK3CA amplification was significantly associated with ECs lacking MMR gene mutations (familial site-specific endometrial cancer).
  • Decreased PTEN expression was more common in ECs (63%) than CRCs (39%), while KRAS mutations were more prevalent in CRCs (27%) than ECs (10%), irrespective of MMR status.
  • PIK3CA alterations frequently co-occurred with PTEN or KRAS changes.

Conclusions:

  • PIK3CA, PTEN, and KRAS alterations play a significant role in the development of familial colorectal and endometrial cancers.
  • These findings expand the understanding of PI3K pathway involvement in human tumorigenesis, extending beyond sporadic cancers.
  • The study highlights specific genetic drivers in familial EC and CRC, offering potential targets for future research and therapeutic strategies.

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