Elvira D'Alessandro

Analysis of microsatellite instability and loss of heterozygosity in keratoacanthoma

We analyzed microsatellite instability (MSI) and loss of heterozygosity (LOH) at 17 microsatellite markers located on chromosomes 2p, 3p, 5q, 6q, 9p, 9q, 17p and 18q in 19 randomly selected keratoacantomas (KAs), in one cutaneous lesion that histologically could not unequivocally be differentiated from squamous cell carcinoma, and in one patient with multiple KAs of longstanding duration. The goals of our study were to determine whether, in a similar manner to some visceral carcinomas, genomic instability could be detected in KAs and to clarify whether molecular analysis might be useful to further characterize KA. MSI was observed in 2 of 21 cases (9.5%) at 5 of 17 loci examined. In one patient with a solitary KA, the presence of MSI and a family history of visceral malignant tumours suggested that the patient might have belonged to a family with Muir-Torre syndrome. In one other MSI+ KA, a definite differential diagnosis in relation to squamous cell carcinoma could not be established. In addition, one sample displayed LOH at 2 of 17 loci analysed whereas in the patient with multiple KAs, LOH at one locus was the only alteration found. In conclusion, the low frequency of MSI and LOH detected in our study suggests that these genetic events are uncommon in KA unless it is associated with a familial disease (e.g. Muir-Torre syndrome) or it has more aggressive histological features.

Cytogenetic follow-up in a case of Sézary syndrome

A cytogenetic follow-up study was performed for a 3-year period on a 70-year-old patient with Sézary syndrome (SS). The results showed formation of hypotetraploid cell clones with 60 to 89 chromosomes and 19 markers, some of which appeared during the period of study and stabilized thereafter. The incidence of these clonal cells increased from 29% to 85% during the follow-up study. The results confirm the presence of hypotetraploid cell clones, especially in the more advanced stages of SS. Moreover, some marker chromosomes in our patient (M2 and M3), derived from chromosome 2, were similar to those observed in SS by other investigators. According to our data and to those in the literature, SS appears to involve preferentially chromosomal regions 2p12-13, 2p21-22, 2q37, 17p13, 13q1, 9q11, 10p13, 14q11, 14q32, 7p1 and, to a lesser extent, 5q and 6q.

Familial centric fission of chromosome 4.

A centric fission of chromosome 4 is described in the proband and his mother, both phenotypically normal. In addition, partial monosomy for the long arm or the short arm or both of chromosome 4 may have been present in two of the probands sibs who died in infancy and childhood, respectively.

Familial paracentric inversion of chromosome 15 (q15q24).

A paracentric inversion of chromosome 15 was observed in the father of two infants who died 29 days and 24 hours, respectively, after birth. The same inversion was found in two sisters of the proband.

Paracentric inversion of chromosome 15(q15q24): description of three families

SummaryThree unrelated families with paracentric inversion of chromosome 15(q15q24) are reported. An additional pericentric inversion of chromosome 9 with breakpoints in p11.2q13 was also observed in one of the three families. Reproductive problems, such as stillbirths, spontaneous abortions and two live-born children with multiple abnormalities, were present.

The human ovarian cancer cell line CABA I: A peculiar genetic evolution

The objective of this study was to study the human ovarian cancer cell line CABA I by means of short tandem repeats (STR) profiling and cytogenetic analysis in order to prevent future misidentification or cross-contamination and verify its stability during in vitro cultivation. To this end, cells at passages 18 and 38 were analyzed using cytogenetic techniques in order to verify possible chromosomal aberrations and the karyotypic evolution of this cell line; GTG-banding and FISH were also performed. For STR analysis, DNA was extracted using the automated extractor MagNA pure and analyzed by means of PowerPlex 16 HS. STR profiles were analyzed by GeneMapper 3.2.1 software. Whereas comparative cytogenetic analysis of CABA I cells at passage 18 and 38 has demonstrated considerable genetic instability, we found that STR profiles were essentially unaltered in both analyzed passages, suggesting that the STR profile is reliable and could be used for the regular authentication of CABA I over time. It should be emphasized, however, that of the 16 loci generally used in human STR profiles, only 3 were properly detectable in CABA I. The data highlight that the CABA I cell line demonstrates an anomalous STR profile that does not fully adjust the criteria currently used for the identification of human cells; in spite of this, it remains stable during the in vitro maintainance. Moreover, the genetic instability of the CABA I cell line overlaps with those observed in vivo in tumor cells, making it a suitable candidate to analyze, in vitro, the peculiar genetic evolution of ovarian cancer cells.

Partial monosomy of 7q32 in a case of de novo rcp(7;15)(q32;q15).

A de novo apparently balanced translocation between chromosomes 7 and 15 with breakpoints in q32 and q15 respectively is reported in a female child. Clinical features included general growth and psychomotor retardation, feeding problems, microcephaly, low set ears, a short neck, and brachydactyly. These findings suggested possible physical or functional partial monosomy of the 7q32 or 15q15 segments. The phenotype of this case is similar to other cases of 7q deletion.