Multiple Tumors in a Child with Germ-Line Mutations inTP53andPTEN

Origin of carcinoma associated fibroblasts

“…We consider the CAFs as part of these cancer microenvironment changes that occur in tissue lesions and serve as precursors for malignant disease. Several hypotheses have been presented for the origin of these altered cells, including standard connective tissue acute phase and stress response, 55,80,81 and fibroblast senescence, [82][83][84][85] reciprocal interactions with the cancer cells, 5,20,[86][87][88][89][90] fibroblast specific somatic mutations, [91][92][93][94][95] differentiation precursors and infiltrating mesenchymal stem cell. 96,97 …”

Homozygous PTEN deletion in neuroblastoma arising in a child with Cowden syndrome

“…Whole PTEN deletion accounts for a minority of Cowden and related Bannayan-Rilvey-Ruvalcaba syndromes [Delnatte et al, 2006]. Neuroblastic tumors have been reported only once in a patient with a PTEN mutation, but together with a TP53 mutation [Plon et al, 2008]. While a co-ocurrence of Cowden syndrome and neuroblastoma could have occurred by chance, several lines of evidence suggest a driving role for PTEN in the present tumor.…”

“…Since PTEN mutation frequently occurs together with other driving oncogenic mutations [Delnatte et al, 2006;Plon et al, 2008], we investigated whether mutations in ALK or PHOX2B could have played such a synergistic role in the present tumor. Direct sequencing of both genes were performed from the tumor DNA as reported elsewhere [Berry-Kravis et al, 2006;JanoueixLerosey et al, 2008].…”

Paediatric ovarian tumours and their associated cancer susceptibility syndromes

“…Plon and colleagues described a child with a JGCT who had a germline mutation in PTEN and TP53 14 . DICER1 somatic hotspot mutations have occasionally been identified in JGCTs, and two cases of JGCT have been associated with DICER1 syndrome,15 but a definitive link between JGCT and DICER1 mutations requires a larger series of cases.…”