Molecular progression of SHH-activated medulloblastomas

Excerpt

Medulloblastoma (MB) comprises four main molecular MB subgroups (WNT, SHH, Group 3 and Group 4) with divergent biology, outcomes and subgroup-specific differences in relapses [1‐6]. Metastatic recurrences are most common in Group 3 and 4 MB, where metastases from a single patient are genetically similar to each other, but highly divergent from the corresponding primary tumor [2‐6]. Local recurrences in the tumor bed are more frequent in SHH-activated tumors but progression-associated molecular aberrations for this MB variant remain unclear [2, 6]. To assess a biological evolution of SHH MB, we analyzed molecular changes appearing during local regrowth of desmoplastic nodular MB (DNMB). Eleven pairs of primary and recurrent DNMB samples were analyzed with DNA- and RNA-based methods. Tumor samples were obtained by resection from three infants, two children, and six adults older than 17 years (all at M0 stage; Suppl. Table). After primary resection, infants received chemotherapy alone, while children and adults were treated according to HIT protocols that included cranio-spinal radiotherapy as well. Event-free survival varied widely for these 11 patients, ranging from 8 to 192 months, with infants on average relapsing earlier than non-infants (11 months vs. 82 months for others); all 11 “secondary” samples were obtained via resection of the local DNMB recurrences. …