Uterine leiomyoma cytogenetics. III. Interphase cytogenetic analysis of karyotypically normal uterine leiomyoma excludes possibility of undetected trisomy 12.

Uterine leiomyoma, a benign tumor that histopathologically is rather homogeneous, was recently characterized cytogenetically. About 40% of the investigated tumors are associated with clonal chromosome abnormalities and five different subgroups have been identified, characterized by trisomy 12, t(12;14)(q14-15;q23-24), del(7q), t(1;2)(p36;p24), and 6p rearrangements. In our survey of 76 cases, trisomy 12 was observed in 10% of the abnormal cases. To exclude a possible underscoring of this abnormality, we reexamined 15 of the cases with normal karyotype by interphase cytogenetics using a chromosome 12 alphoid DNA probe.     

Chromosome rearrangements in two uterine sarcomas

Cytogenetic analysis of short-term cultures from two uterine sarcomas revealed clonal chromosome abnormalities in both cases. A locally recurrent mixed mesodermal tumor had the karyotype 61,XX,+2,+3,+del(5)(q11),+6,+7,+del(7)(q32),+8,+8,+8,+10, -11,-11,+der(11)t(1;11)(q12;p15),+der(11)t(1;11)(q12;p15),+der(11)t(1;11)(q12;p15),+del(12)(q14q21),+13,+15,del(17)(q23),+20. The other tumor, a lung metastasis from a uterine leiomyosarcoma, had several karyotypically abnormal clones. Two of them consisted of highly aberrant cells with modal chromosome numbers of 82 and 153, respectively, but because of insufficient quality the complex anomalies could not be identified. Various chromosomal changes that included translocations, deletions, insertions, and numerical rearrangements (always with extra chromosome 7 material) were identified in pseudo- or near-diploid cells, resulting in nine additional cytogenetically abnormal clones.     

Uterine leiomyoma cytogenetics. II. Report of forty cases

Chromosome analysis of 40 cultured uterine leiomyomas revealed the presence of clonal changes in 32.5% of them, confirming the cytogenetic heterogeneity within this type of tumor, mostly referable to a few cytogenetic subgroups. Preferential involvement of 12q14-15 and 14q23-24 bands in reciprocal and complex translocations was most commonly observed. Deletions of chromosome 7 and changes of chromosomes 1, 2, and to a lesser extent, chromosomes 19 and 22 were also found. Constitutional karyotype of patients bearing tumors with karyotypic abnormalities was examined. In one patient, two cells were found with t(12;14)(q14-15;q23-24) translocation and two with del(14)(q13q23-24). The latter rearrangement was also present as a clonal change in the tumor.     

Cytogenetic studies of primary cultures of esophageal squamous cell carcinoma

Cytogenetic analysis was performed on primary cultures of 21 squamous cell carcinomas of the esophagus (SCCE). Seven cases exhibited mosaic clonal chromosome abnormalities distributed as follows: two contained tetraploid cell populations, one with t(3;7)(p21;q11); two showed loss of the Y chromosome, one with double minutes; single cases demonstrated der(11)t(4;11)(q?27;q23); add(1)(p35) and del(4)(p12); and del(7)(p13), del(7)(q22q34), and der(11)t(7;11)(p?15;p?13). The remaining 14 cases had apparently normal karyotypes, possibly derived from stromal elements. These results demonstrate numerical abnormalities and the multiple occurrence of rearrangements involving chromosomes 7 and 11 in SCCE.     

Complex karyotypic changes, including rearrangements of 12q13 and 14q24, in two leiomyosarcomas

Cytogenetic investigation of short-term cultures from two leiomyosarcomas revealed complex karyotypic changes in both cases. The first tumor, a subcutaneous leiomyosarcoma of the knee, had the karyotype 70-80,XY, +X, +Y, +1, +1, +2, +2, +3, +3, +4, +4, +7, +7, +8, +8, +9, +10, +15, +15, +16, +16, +18, +19, +20, +21, +21, +22, +22,t(?;5)(5;21)(?;q35p11;q11), t(?;5)(5;21)(?;q35p11;q11), +del(11)(q22),der(13)t(12;13)(q13;q22),der(14)t(9;14)(p11;p11), +14p+, +t(20;?)(q13;?), +t(20;?)(q13;?), +2 mar. A polyploidized clone with 120-150 chromosomes was also observed. DNA flow cytometry revealed only one abnormal peak, corresponding to a DNA index of 1.76. The other tumor, a uterine leiomyosarcoma, had the karyotype 61-67, X, -X, +1, +3, +5, +6, +7, +8, +9, +12, +13, +15, +t(1;1)(p32;q32), +der(1)t(1;8)(p13;q11), +del(2)(p11), +del(2)(q22), +del(2)(q22), +del(3)(p13), +i(5p),t(8;14)(q24;q24), +der(8)t(8;14) (q24;q24), +del(10)(p12),der(11)t(11;15)(p15;q11),t(16;?)(p13;?),t(16;?)(q24;?), der dic(17) (17pter----cen----17q25::hsr::17q25----cen----17pte r), +t(19;?)(p13;?), +der dic(20)(20pter----cen----20q12::hsr::20q12----cen----+ ++20pter), +mar. The DNA index was 1.59. The finding in these leiomyosarcomas of rearrangements of the same regions of chromosomes 12 and 14 that are involved in the tumor-specific t(12;14)(q14-15;q23-24) of uterine leiomyoma indicates that the same genes in 12q and 14q might be important in the pathogenesis of benign and malignant smooth muscle tumors.     

Cytogenetic study of a spindle-cell rhabdomyosarcoma of the parotid gland

The cytogenetic analysis of a spindle-cell rhabdomyosarcoma of the parotid gland in a 6-year-old boy is reported. The tumor cells showed an abnormal karyotype with a hypotriploid modal chromosome number and clonal structural rearrangements affecting chromosomes 1, 8, 12, 21, and 22. The tumor karyotype was: 59, XY, -1, -3, -4, -5, -6, +8, +8, +del(8)(q22q24), -9, -10, del(12)(q13), -15, -16, -17, -18, der(21)t(12;21)(p11;p11), -22, der(22)t(1;22)(q12;p11).     

Ring formation and structural rearrangements of chromosome 1 as secondary changes in uterine leiomyomas with t(12;14)(q14-15;q23-24)

Cytogenetic analysis of short-term cultures from two uterine leiomyomas revealed, in addition to the primary abnormality, the reciprocal translocation t(12;14)(q14-15;q23-24), secondary structural changes that in both cases included ring chromosomes and rearrangements of chromosome 1. One tumor had the karyotype 46,XX,r(1)(p34q32),ins(8;9)(q13;q13q22),t(12;14)(q14-15;q23- 24). Massive numerical rearrangements were found in the second leiomyoma, with chromosome numbers ranging from 47 to 92. In spite of this variability, two main cell populations could be discerned, one near-diploid, the other hypotetraploid, with most mitoses having chromosome numbers between 80 and 88. These findings were corroborated by flow cytometry, which revealed two peaks corresponding to DNA indexes of 0.97 and 1.77. The structural abnormalities t(1;1)(p31;q44) and t(12;14)(q14-15;q23-24) were present in all karyotypically abnormal cells, and one or more unidentified ring chromosomes were observed in most of the hypotetraploid mitoses. In no cells were double copies of the t(1;1) and t(12;14) rearrangements detected. The similarity between the secondary changes in the cases reported here suggests that clonal evolution in uterine leiomyoma is nonrandom.     

Non-random chromosome rearrangements in adenoid cystic carcinoma of the salivary glands

The chromosomal findings in 10 adenoid cystic carcinomas (ACC) of the salivary glands are described. Clonal numerical deviations as the sole anomaly were detected in four cases and structurally rearranged stemlines and sidelines in four cases. An apparently identical t(6;9)(q23;p21) was found in two tumors; in one case the translocation was part of the abnormal stemline and in the other case it was the sole anomaly in a single variant cell. A similar or identical t(6;9)(q21-24;p13-23) has recently been reported in three of 15 previously published cases of ACC. The three remaining tumors with abnormal stemlines all had rearrangements of chromosome 9, including t(1;9)(q21;p21-22), der(9)i(9)(q10)inv(9)(q12q 13), and der(X)t(X;9)(p21;p22-23), respectively. The latter case also had a t(17;18)(p12;q11.2) that was common to both abnormal clones present in this tumor. In addition to other abnormalities, the clone with der(X)t(X;9) also showed a del(6)(q13q21). In two cases fluorescence in situ hybridization (FISH) was used for further characterization of the marker chromosomes. A survey of the present findings together with previous results from 15 ACC clearly demonstrates that rearrangements of 6q21-24 (deletions or translocations in 11 cases), 9p13-23 (translocations in seven cases), and 17p12-13 (translocations in three cases) are recurrent, and often primary, in ACC, and that the t(6;9)(q21-24;p13-23), found in five tumors, is a non-random, primary aberration. Genes Chromosom Cancer 10:115–121 (1994). © 1994 Wiley-Liss, Inc.     

A specific translocation,t(12;14)(q14–15; q23–24), characterizes a subgroup of uterine leiomyomas

We have cytogenetically investigated short-term cultures initiated from 34 uterine leiomyomas, all of which were histologically completely benign. Clonal chromosome abnormalities were detected in five cases, a normal female complement in 22, whereas, in the remaining seven tumors no karyotype could be established. Apparently identical reciprocal translocations, t(12;14)(q14–15;q23–24), were found as the sole abnormality in four tumors. The fifth abnormal case contained a t(2;14)(p11;p11). We conclude that chromosome aberrations may be found in myomas of the uterus, and that t(12;14)(q14–15;q23–24) characterizes a subset of these tumors.     

Parallel karyotypic evolution and tumor progression in uterine leiomyoma

Cytogenetic evidence of clonal evolution was detected in five uterine leiomyomas. In two tumors, two clones were found, the third tumor had four, the fourth had nine, and the fifth had 12 clones. The first tumor had trisomy 12 as the primary anomaly and a sideline that also contained a del(7)(q21q31). Both clones of the second tumor had three structural changes in common but differed by the presence in the more advanced clone of an inv(7)(q31q34). Two cytogenetically unrelated pairs of clones were seen in the third tumor. One clone had a stemline of 46 and an r(1); a sideline had developed through duplication of this clone. The other pair had a del(7)(q21q31) in common. The last two tumors both had t(12;14)(q14-15;q23-24) as the primary abnormality. They also had a high frequency of telomeric associations that involved certain chromosome arms only. One of the secondary changes in the fourth tumor was a del(7)(q21q31); the principal secondary change in the fifth case was a ring chromosome 1 of variable size in the different clones. The analysis of these five uterine leiomyomas and the collation of the results with previously obtained data lead us to conclude that del(7)(q21q31) is secondary to t(12;14) and + 12 in this tumor type, and that ring formation involving chromosome 1 material, often with duplication of segments, is a common phenomenon during clonal evolution. The fact that the tumors were classified as cellular and had an increased mitotic rate indicates a parallel development between histologically detectable tumor progression and cytogenetically recognizable clonal evolution in uterine leiomyomas.     

Chromosome analysis of 96 uterine leiomyomas

From September 1989 to May 1990, we attempted cytogenetic analysis on 96 uterine leiomyomas removed from 64 women. Of the 90 tumors in which analysis was successful, 59 had a normal karyotype while 31 had clonal abnormalities. The most common aberration (13 tumors) was 7q-, mostly del(7)(q21.2q31.2); in two tumors with +12 and t(12;14) as the primary abnormalities, the 7q- was obviously a secondary change since it was found only in a subclone. A t(12;14)(q14-15;q23-24) was detected in two tumors, complex aberrations involving both 12q14-15 and 14q23-24 were also present in two, and rearrangements of 12q without concomitant 14q changes were seen in another two myomas. Rearrangements of 6p were present in five tumors, and trisomy 12 was found in two. More than one abnormality could be detected in 17 leiomyomas. Evidence of clonal evolution in the form of subclones was found in eight tumors, all of which were cellular and had histologically detectable mitotic activity. In addition to their clonal complexity, these myomas also frequently exhibited clonal telomeric associations (four tumors) and ring chromosome formation (three tumors; twice affecting chromosome 1). Monosomy 22 occurred as a secondary abnormality in three tumors; it, too, may reflect a preferred pathway in the karyotypic evolution of uterine leiomyomas.     

Karyotypic findings in two cases of male breast cancer

Male breast cancer is uncommon; so far, only 10 cases with chromosome banding analysis have been published. We report the cytogenetic findings of two invasive breast cancers in two Caucasian men lacking a history of familial breast cancer and more than 70 years of age. Both had ductal carcinomas with lymphangiosis carcinomatosa and positive lymph nodes at diagnosis. Strong expression of estrogen receptor, weak expression of progesterone receptor, and lack of expression of androgen receptor by both tumors were demonstrated by immunohistochemistry, as well as lack of expression of p53 and C-ERB-B-2. The karyotypes were 45 approximately 46,XY,-Y[4],-7[2],+8[2],t(8;12)(q21;q24)[3], del(9)(q22)[3],del(11)(p11p14)[5],del(18)(q21)[7], t(19;20)(p10;q10)[8] [cp13] and 61 approximately 69,XXXY,-Y[3], del(2)(p21)[4],del(3)(p22q26)[3],-4,-4[5],+5,+5[5], dic(5;11)(p14;q23)[3],del(6)(q23)[4],del(8)(p21)[3],-9[4],-11[4],+ i(12)(p10)[4],-16[3],del(17)([13)[5],del(18)(q21)[4],+19[5], +20[4][cp7], respectively. Although the available data on male breast cancer are still very limited, our findings confirm that gain of an X chromosome, loss of the Y chromosome, gain of chromosome 5, and loss of material from chromosomes 17 and 18 are nonrandom aberrations in male breast cancer. Trisomy 8, characteristic of ductal carcinomas, was found in one case.     

Specific subtelomere loss on chromosome der(11)t(3;11)(q23;q23)x2 in anaplastic thyroid cancer cell line OCUT-1

One of the most aggressive human malignancies, anaplastic thyroid carcinoma (ATC), has an extremely poor prognosis that may be explained by its genomic instability. We hypothesized that the very rapid cell turnover observed in ATC might accelerate telomere shortening and chromosomal instability associated with tumor cell malignancy. To compare and measure chromosomal aberrations and telomere shortening in the anaplastic thyroid cancer cell line OCUT-1, we applied quantitative fluorescence in situ hybridization (Q-FISH) techniques. In all 15 metaphases studied, telomere length estimates from Q-FISH of chromosomes in ATC were shorter than those of a fibroblast cell line derived from the stroma adjacent to the carcinoma. OCUT-1 cells display several chromosomal abnormalities, but have a near-normal chromosome complement of 46, XX, making it easy to analyze the karyotype. The karyotype showed 50, XX, +7, +11, der(11)t(3;11)(q23;q23)x2, del(12)(p11.2p12), +20, +1mar. We analyzed carefully the abnormalities in karyotype of OCUT-1 associated with telomere shortening on each chromosome and expression of subtelomeres. Telomere lengths in the q-arms of the abnormal chromosome del(12)(p11.2p12) were shorter than the average length in the q-arms of the normal chromosome 12 in OCUT-1. Subtelomeres on the abnormal chromosome der(11)t(3;11)(q23;q23)x2 also showed loss of signals on 11p, but there was no loss of signals in the cytogenetically normal trisomies 7 and 20 or the abnormal chromosome del(12)(p11.2p12). Subtelomeres of 3q had eight signals, one pair remaining in place on 3q and another pair on the abnormal 11p. Our findings suggest that telomere shortening and subtelomere loss are correlated with genetic instability in this anaplastic thyroid carcinoma cell line.     

Endometrial stromal sarcoma with clonal complex chromosome abnormalities. Report of a case and review of the literature.

Only eleven endometrial stromal sarcomas (ESS) with clonal chromosomal abnormalities have been reported in the literature. Of these, four have been reported to harbor the t(7;17) translocation. We report here an additional ESS that exhibited clonal complex chromosome abnormalities not described earlier: 38,XX,-1,del(1)(q11),-2,add(2)(p13),-3,der(4)add(4)(p12)psu dic(4;14)(q35;q11.2), add(6)(p21.3),add(7)(q22),del(7)(p11.2p13),-8,-9,add(9)(q34),- 10,add(10)(q24),-11,-11,ins(12;?) (q13;?),-14,-14,-15,ins(15;?)(q22;?),add(16)(q22),add(17)(q11.2),- 18,der(18)t(7;18)(q11.2;p11.2),-19, add(20)(p13),add(21)(p11.2),-22,add(22)(p11.2),+6mar in metaphase cells from primary short-term culture.     

Frequency of structural abnormalities of the long arm of chromosome 12 in myelofibrosis with myeloid metaplasia

Among cytogenetic studies of 205 patients diagnosed as myelofibrosis with myeloid metaplasia, we found seven cases with structural abnormalities of the long arm of chromosome 12. The karyotype showed six balanced translocations, that is, t(4;12)(q33;q21), t(5;12)(p14;q21), t(1;12)(q22;q24), t(12;17)(q24;q11), t(7;12) (p11;q24), and t(1;12)(p12;q24), as well as other cytogenetic abnormalities such as del(12)(q21;q24) and inv(12) (p12q24). Some isolated cases involving the 12q21 region have also been described in the literature. Importance of rearrangement of chromosome 12 in 12q21 or 12q24 is underlined by the authors suggesting a proto-oncogene accountable mechanism of leukemogenesis.     

Uterine leiomyoma cytogenetics

Uterine leiomyoma--a benign smooth muscle tumor--has recently been found to contain tumor-specific chromosome aberrations. Although only normal karyotypes were detected in 50 to 80% of cytogenetically investigated tumors, 104 leiomyomas with karyotypic aberrations have already been reported. At least four cytogenetically abnormal subgroups have been identified thus far, characterized by rearrangements of 6p, del(7)(q21.2q31.2), +12, and t(12;14)(q14-15;q23-24). The remaining abnormal tumors have had various nonrecurrent anomalies. Secondary karyotypic rearrangements, sometimes including ring chromosomes, have been found in one-third and reflect clonal evolution. Occasional leiomyomas have contained multiple numerical and structural rearrangements. Though benign, these cytogenetically grossly aberrant tumors often displayed more atypical histological features than are usually seen in leiomyoma. Multiple leiomyomas have been investigated from 69 patients, with detection of chromosome anomalies in at least two separate tumors from the same uterus in ten cases. In half of these patients unrelated aberrations were found in different leiomyomas from the same uterus. On other occasions the aberrations were identical, indicating that although some uterine leiomyomas originate independently, others may develop by intra-myometrial spreading from a common neoplastic clone. Some common features are discernible between the karyotypic pictures of uterine leiomyoma and angioleiomyoma; rearrangements of 6p, 13q, and 21q have been described in both tumor types. The cytogenetic similarities so far detected between leiomyoma and the malignant muscle tumors--leiomyosarcoma and rhabdomyosarcoma--are few and may be fortuitous. The cytogenetic profiles of leiomyoma and lipoma are strikingly similar; both tumor types have nonrandom rearrangements of 12q13-15, t(12;14) in leiomyoma and t(3;12) in lipoma, as well as variant rearrangements of the same 12q segment. Both also have cytogenetic subgroups characterized by changes in 6p and ring chromosomes. Finally, karyotypic similarities exists also between leiomyoma and pleomorphic adenoma of the salivary gland, which includes a subset of tumors with anomalies of 12q13-15, and with myxoid liposarcoma, which has t(12;16)(q13;p11) as a tumor-specific rearrangement.     

Recessive cancer genes in meningiomas? An analysis of 31 cases

Cytogenetic studies on 31 human meningiomas revealed clonal abnormalities in 14 of them. Monosomy 22 was present in three cases as the only abnormality, and in five it was associated with monosomy 18, monosomy 14, loss of X, loss of Y, and trisomy 20, respectively. We found a number of rearrangements involving chromosome #22: an i psu dic(22)(pter----q11::q11----pter) in two cases and a t(18;22)(q12;q11) in another case. Two cases showed a complex translocation involving #7 and #14: t(2;7;14)(q23;q36;q22) and t(1;7;14)(q25;q32;q22), respectively. Other clonal chromosome abnormalities were del(1p) (present in two cases); der(9)t(9;?)(q34;?); der(7)t(7;?)(q31;?); der(22)t(22;?)(q11;?); and a 9p+ chromosome. The relevance for the pathogenesis of human meningiomas of these chromosome anomalies is also discussed with reference to the previous literature. The possible involvement of recessive cancer genes present on the long arm of chromosome #22 is also discussed.     

Karyotypic characterization of urinary bladder transitional cell carcinomas

Samples from 34 primary transitional cell carcinomas (TCCs) of the bladder were short-term-cultured and processed for cytogenetic analysis after G-banding of the chromosomes. Clonal chromosome abnormalities were detected in 27 tumors and normal karyotypes in 3, and the cultures from 4 tumors failed to grow. Losses of genetic material were more common than gains, indicating that loss of tumor suppressor genes may be of major importance in TCC pathogenesis. There was no clonal heterogeneity within individual tumors, consonant with the view that TCCs are monoclonal in origin. The most striking finding was the involvement of chromosome 9 in 92% of the informative cases, as numerical loss of one chromosome copy in 15 cases, but as structural rearrangement in 8. The changes in chromosome 9 always led to loss of material; from 9p, from 9q, or of the entire chromosome. A total of 16 recurrent, unbalanced structural rearrangements were seen, of which del(1)(p11), add(3)(q21), add(5)(q11), del(6)(q13), add(7)(q11), add(11)(p11), i(13)(q10), del(14)(q24), and i(17)(q10) are described here for the first time. The karyotypic imbalances were dominated by losses of the entire or parts of chromosome arms 1p, 9p, 9q, 11p, 13p, and 17p, loss of an entire copy of chromosomes 9, 14, 16, 18, and the Y chromosome, and gains of chromosome arms 1q and 13q and of chromosomes 7 and 20. The chromosome bands and centomeric breakpoints preferentially involved in structural rearrangements were 1q12, 2q11, 5q11, 8q24, 9p13, 9q13, 9q22, 11p11, and 13p10. Rearrangements of 17p and the formation of an i(5)(p10) were associated with more aggressive tumor phenotypes. There was also a general correlation between the tumors' grade/stage and karyotypic complexity, indicating that progressive accumulation of acquired genetic alterations is the driving force behind multistep bladder TCC carcinogenesis.     

Quantitative acute leukemia cytogenetics.

Using literature data on cytogenetic abnormalities in 3,612 cases of acute myeloid leukemia (AML) and 1,551-cases of acute lymphocytic leukemia (ALL), we have attempted to quantify the information value of finding the typical ALL- and AML-associated chromosome aberrations. Sensitivity, specificity, and predictive value of finding or not finding a given aberration were calculated for several diagnostic scenarios: for the differential diagnosis between ALL and AML when the patient is known to have acute leukemia, for the differential diagnosis among AML FAB subtypes in a patient with known AML, and for the differential diagnosis between ALL FAB subtypes in a patient with known ALL. The specificities were generally high, close to 1. The highest sensitivities in AML were found for +8, t(15;17)(q22;q11), t(8;21)(q22;q22), and -7 (all greater than 0.1), and in ALL for t(9;22)(q34;q11), t(4;11)(q21;q23), and +21 (again all greater than 0.1). In the AML subtypes, the highest sensitivities were 0.89 for t(15;17)(q22;q11) in M3, followed by 0.40 for t(8;21)(q22;q22) in M2, 0.30 for inv(16)(p13q22)/del(16)(q22)/t(16;16)(p13;q22) in M4, and 0.16 for t(9;11)(p21;q23) in M5. In the ALL subtypes, the highest sensitivities were 0.71 and 0.11 for t(8;14)(q24;q32) and t(8;22)(q24;q11), respectively, in L3, 0.23 for t(9;22)(q34;q11) in L2, and 0.18 and 0.13 for +21 and t(4;11)(q21;q23), respectively, in L1. The highest (1.0) positive predictive values in the AML versus ALL comparison were found for t(1;3)(p36;q21), inv(3)(q21q26), t(6;9)(p23;q34), t(7;11)(p15;p15), t(8;16)(p11;p13), t(8;21)(q22;q22), t(15;17)(q22;q11), and, as sole anomalies, for +4, +9, and +11. In the reverse comparison, ALL versus AML, positive predictive values of 1.0 were found for t(1;14)(p32-34;q11), dup(I)(q12-21q31-32), t(2;8)(p12;q24), t(8;14)(q24;q32), t/dic(9;12)(p11-12;p11-13), t(10;14)(q24;q11), and t(11;14)(p13;q11). Among the AML subgroups, the highest predictive values were: 1.0 for M3 if t(15;17), 0.91 for M2 if t(8;21), 0.86 for M4 if inv/del(16)/t(16;16), and 0.82 for M5 if t(9;11). Among the ALL subtypes, positive predictive values of greater than 0.8 were reached only for the L3-associated aberrations t(2;8) (1.0), t(8;14) (0.95), t(8;22) (0.87), and dup(I) (0.80). The highest negative predictive values were in AML 0.98 that the disease is not M3 if t(15;17) is not found, and in ALL 0.96 that the patient does not have L3 if a t(8;14) is not detected.