Cytomegalovirus Immunity after Vaccination with Autologous Glioblastoma Lysate

onset breast cancer in two aunts.The patient's mother had a cerebellar astrocytoma, two vaginal tumors, and a malignant nevus (Fig. 2A).The germ-line PTEN genes of the child and her father had a base change, c.334C→G.Although this change putatively encodes an L112V missense mutation, PTEN messenger RNA (mRNA) analysis instead revealed activation of a cryptic splice site (Fig. 2B).The germ-line TP53 gene in the proband, her sister, and her mother contained an R282W deleterious missense mutation.Thus, the proband had inherited deleterious mutations in both TP53 and PTEN.In tumors from patients with the Li-Fraumeni syndrome or Cowden's syndrome, there is often somatic mutation or silencing of the second copy of the tumor-suppressor gene. 3 The granulosa-cell tumor, xanthoastrocytoma, and multiple liposarcoma samples from our proband revealed no somatic mutations in TP53 or PTEN.Loss of heterozygosity was not detected in TP53, but it was detected in PTEN in the granulosa-cell tumor and the liposarcoma specimen after chemotherapy (but not in specimens from the initial resection and lung metastasis) (Fig. 2C).The finding that several of the patient's tumors did not have loss of heterozygosity or somatic mutations was also reported for tumors from a mouse model that was doubly heterozygous for p53 and Pten mutations. 4 The types and numbers of tumors that developed in the proband by 4 years of age are not typical of the Li-Fraumeni syndrome or Cowden's syndrome, and four malignant conditions are expected to develop in only 2% of patients with the Li-Fraumeni syndrome. 1,5 This tumor spectrum may reflect the intricate coregulation of the TP53 and PTEN proteins. 4 Clinically, it may be useful to sequence in parallel multiple cancerassociated genes of patients with unusual cancer phenotypes.