Segmental chromosomal aberrations and ploidy (neuroblastoma)

What is measured: the genomic profile of the tumour, numerical against segmental. How: SNP array or array comparative genomic hybridisation on tumour DNA (MLPA or FISH for 1p and 11q where arrays are unavailable), flow cytometry for the DNA index (ploidy), and FISH for MYCN. Numerical-only profiles (whole-chromosome gains and losses, hyperdiploid, DNA index above 1) are favourable, especially in infants; segmental aberrations (11q deletion in 30 to 40 percent, 1p deletion in about 30, 17q gain in about half, plus 3p and 4p loss and 1q and 2p gain) mark a higher relapse risk, 11q loss and MYCN amplification being almost mutually exclusive; ATRX loss and TERT rearrangements appear in older children. The INRG classifier combines MYCN, 11q and ploidy with age, INRG stage and INPC histology. What a result changes: infants with stage MS or L2 disease and no segmental aberration are observed or given minimal chemotherapy; L2 disease with 11q deletion or other segmental change moves to intermediate risk with more chemotherapy in the SIOPEN LINES and COG protocols; diploidy in an infant with metastatic disease raises the risk group; an ALK mutation now adds lorlatinib to high-risk therapy (COG ANBL1531). Where it matters: neuroblastoma and its low, intermediate and high-risk pages.