$ cat pm_11109568_file1.txt
A:?:?:A4:?
B:?:?:B4:?
C:?:?:C4:?
D:?:?:D4:?

##</code><code>##

$ cat pm_11109568_file2.txt
C,?,?,?,?,W6,?
X,?,?,D,?,X6,?
Y,?,?,?,?,Y6,B
Z,?,?,?,?,Z6,?

##</code><code>##

#!/usr/bin/env perl

use strict;
use warnings;
use autodie;

my ($file1, $file2, $file3) = qw{
    pm_11109568_file1.txt
    pm_11109568_file2.txt
    pm_11109568_file3.txt
};

my %search;

{
    open my $fh1, '<', $file1;
    while (<$fh1>) {
        my ($field1, $field4) = (split /:/)[0,3];
        $search{$field1} = $field4;
    }
}

my $re_alt = join '|', keys %search;
my $re = qr{(?:^|,)($re_alt)(?:,|$)};

{
    open my $fh3, '>', $file3;
    open my $fh2, '<', $file2;
    while (<$fh2>) {
        if (/$re/) {
            my $key = $1;
            my @fields = split /,/;
            $fields[5] = $search{$key};
            print $fh3 join ',', @fields;
        }
        else {
            print $fh3 $_;
        }
    }
}

##</code><code>##

$ cat pm_11109568_file3.txt
C,?,?,?,?,C4,?
X,?,?,D,?,D4,?
Y,?,?,?,?,B4,B
Z,?,?,?,?,Z6,?