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I would suspect the following one to be due to incorrect
handling of EXTENDED_ARG -- it's from a PyPy test about that:

longexpr = 'x = x or ' + '-x' * 2500
code = '''
def f(x):
    %s
    %s
    %s
    %s
    %s
    %s
    %s
    %s
    %s
    %s
    while x:
        x -= 1
        # EXTENDED_ARG/JUMP_ABSOLUTE here
    return x
''' % ((longexpr,)*10)

exec code
f(5)
SystemError: unknown opcode

dis.dis() shows that the target of both the SETUP_LOOP and
the JUMP_IF_FALSE at the start of the loop are wrong.