Somatic PTPN11 mutations in childhood acute leukemia. (A) Representative DHPLC profiles showing the occurrence of missense mutations in 5 children with B-cell precursor ALL; in all cases, mutations were observed at diagnosis (top), but were undetectable during remission, after 33 (middle) and 78 (bottom) days of follow-up. Corresponding nucleotide changes and electropherograms are also shown. (B) DHPLC profiles, and corresponding nucleotide change and electropherogram, showing the 215C>T substitution in one case with FAB-M5a identified at diagnosis (top) and relapse (bottom), but not during remission (middle). (C) Location of SHP-2 mutated residues in childhood acute leukemia. Exposed surface or Cα trace of N-SH2 (blue), C-SH2 (magenta), and PTP (orange) domains, and N-SH2/CSH2 and C-SH2/PTP linkers (gray) of the catalytically inactive conformation of SHP-2.²⁹  The views are rotated to show the interdomain interacting surfaces and the exposed residues of the N-SH2 (left) and PTP (right) surfaces. Mutated N-SH2 residues (Asn58, Asp61, Glu69, Ala72, and Glu76) are indicated in red; mutated PTP residues (Pro491, Ser502, Thr507, and Gln510) are indicated in green. SHP-2 domain organization is shown in the boxed area. The numbers below the domain structure indicate the amino acid boundaries of those domains. Dots above the domain structure refer to number of cases with mutations documented in this study.