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Molecular cytogenetic analysis of follicular lymphoma (FL) provides detailed characterization of chromosomal instability associated with the t(14;18)(q32;q21) positive and negative subsets and histologic progression

Nanjangud G.a · Rao P.H.e · Teruya-Feldstein J.b · Donnelly G.c · Qin J.d · Mehra S.a · Jhanwar S.C.a · Zelenetz A.D.c · Chaganti R.S.K.a, c
aCell Biology Program, and the Departments of bPathology, cMedicine, and dEpidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY; eDepartment of Pediatrics, Texas Children’s Cancer Center, Baylor College of Medicine, Houston, TX (USA) Cytogenet Genome Res 118:337–344 (2007) (DOI:10.1159/000108318)

Abstract

We analyzed a cohort of 61 follicular lymphomas (FL) with an abnormal G-banded karyotype by spectral karyotyping (SKY) to better define the chromosome instability associated with the t(14;18)(q32;q21) positive and negative subsets of FL and histologic grade. In more than 70% of the patients, SKY provided additional cytogenetic information and up to 40% of the structural abnormalities were revised. The six most frequent breakpoints in both SKY and G-banding analyses were 14q32, 18q21, 3q27, 1q11–q21, 6q11–q15 and 1p36 (15–77%). SKY detected nine additional sites (1p11–p13, 2p11–p13, 6q21, 8q24, 6q21, 9p13, 10q22–q24, 12q11–q13 and 17q11–q21) at an incidence of >10%. In addition to the known recurring translocations, t(14;18)(q32;q21) [70%], t(3;14)(q27;q32) [10%], t(1;14)(q21;q32) [5%] and t(8;14)(q24;q32) [2%] and their variants, 125 non-IG gene translocations were identified of which four were recurrent within this series. In contrast to G-banding analysis, SKY revealed a greater degree of karyotypic instability in the t(14;18) (q32;q21) negative subset compared to the t(14;18)(q32;q21) positive subset. Translocations of 3q27 and gains of chromosome 1 were significantly more frequent in the former subset. SKY also allowed a better definition of chromosomal imbalances, thus 37% of the deletions detected by G-banding were shown to be unbalanced translocations leading to gain of genetic material. The majority of recurring (>10%) imbalances were detected at a greater (2–3 fold) incidence by SKY and several regions were narrowed down, notably at gain 2p13–p21, 2q11–q21, 2q31–q37, 12q12–q15, 17q21–q25 and 18q21. Chromosomal abnormalities among the different histologic grades were consistent with an evolution from low to high grade disease and breaks at 6q11–q15 and 8q24 and gain of 7/7q and 8/8q associated significantly with histologic progression. This study also indicates that in addition to gains and losses, non-IG gene translocations involving 1p11–p13, 1p36, 1q11–q21, 8q24, 9p13, and 17q11–q21 play an important role in the histologic progression of FL with t(14;18)(q32;q21) and t(3q27).

 

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