title: PIK3CA mutations in in situ and invasive breast carcinomas.
abstract: The PIK3 signaling pathway has been identified as one of the most important and most frequently mutated pathways in breast cancer. Somatic mutations in the catalytic subunit of PIK3CA have been found in a significant fraction of breast carcinomas, and it has been proposed that mutant PIK3CA plays a role in tumor initiation. However, the majority of primary human tumors analyzed for genetic alterations in PIK3CA have been invasive breast carcinomas and the frequency of PIK3CA mutations in preinvasive lesions has not been explored. To investigate this, we sequenced exons 9 and 20 of PIK3CA in pure ductal carcinoma in situ (DCIS), DCIS adjacent to invasive carcinoma, and invasive ductal breast carcinomas. In a subset of cases, both in situ and invasive areas were analyzed from the same tumor. We found that the frequency of PIK3CA mutations was essentially the same ( approximately 30%) in all three histologic groups. In some cases, in situ and invasive areas of the same tumor were discordant for PIK3CA status, and in two cases in which multiple invasive and adjacent in situ areas within the same tumor were analyzed independently, we detected intratumor heterogeneity for PIK3CA mutations. Our results suggest that mutation of PIK3CA is an early event in breast cancer that is more likely to play a role in breast tumor initiation than in invasive progression, although a potential role for exon 9 mutations in the progression of a subset of DCIS cases cannot be excluded.
authors.affiliation: Department of Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Miron
authors.forename: Maria
authors.initials: M
authors.lastname: Varadi
authors.forename: Daniel
authors.initials: D
authors.lastname: Carrasco
authors.forename: Hailun
authors.initials: H
authors.lastname: Li
authors.forename: Lauren
authors.initials: L
authors.lastname: Luongo
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Park
authors.forename: Eun Yoon
authors.initials: EY
authors.lastname: Cho
authors.forename: Gretchen
authors.initials: G
authors.lastname: Lewis
authors.forename: Sarah
authors.initials: S
authors.lastname: Kehoe
authors.forename: J Dirk
authors.initials: JD
authors.lastname: Iglehart
authors.forename: Deborah
authors.initials: D
authors.lastname: Dillon
authors.forename: D Craig
authors.initials: DC
authors.lastname: Allred
authors.forename: Laura
authors.initials: L
authors.lastname: Macconaill
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gelman
authors.forename: Kornelia
authors.initials: K
authors.lastname: Polyak
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002278:Carcinoma in Situ / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D005091:Exons; D005260:Female; D006801:Humans; D009154:Mutation; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human